Patent Publication Number: US-2005131222-A1

Title: Nucleotide sequence of the haemophilus influenzae Rd genome, fragments thereof, and uses thereof

Description:
STATEMENT REGARDING FED SPONSORED R &amp; D  
      Part of the work performed during development of this invention utilized U.S. Government funds. The government may have certain rights in this invention. NIH-5R01GM48251. 
    
    
     REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX  
      This application refers to a “Sequence Listing” listed below, which is provided as an electronic document on two identical compact discs (CD-R), labeled “Copy 1” and “Copy 2.” These compact discs each contain the file “PB186P2C1D2.5T25.txt” (2,385,078 bytes, created on Nov. 5, 2004), which is hereby incorporated in its entirety herein.  
     FIELD OF THE INVENTION  
      The present invention relates to the field of molecular biology. The present invention discloses compositions comprising the nucleotide sequence of  Haemophilus influenzae , fragments thereof and usage in industrial fermentation and pharmaceutical development.  
     BACKGROUND OF THE INVENTION  
      The complete genome sequence from a free living cellular organism has never been determined. The first mycobacterium sequence should be completed by 1996, while  E. coli  and  S. cerevisae  are expected to be completed before 1998. These are being done by random and/or directed sequencing of overlapping cosmid clones. No one has attempted to determine sequences of the order of a megabase or more by a random shotgun approach.  
       H. influenzae  is a small (approximately 0.4×1 micron) non-motile, non-spore forming, germ-negative bacterium whose only natural host is human. It is a resident of the upper respiratory mucosa of children and adults and causes otitis media and respiratory tract infections mostly in children. The most serious complication is meningitis, which produces neurological sequelae in up to 50% of affected children. Six  H. influenzae  serotypes (a through f) have been identified based on immunologically distinct capsular polysaccharide antigens. A number of non-typeable strains are also known. Serotype b accounts for the majority of human disease.  
      Interest in the medically important aspects of  H. influenzae  biology has focused particularly on those genes which determine virulence characteristics of the organism. A number of the genes responsible for the capsular polysaccharide have been mapped and sequenced (Kroll et al.,  Mol. Microbiol.  5(6):1549-1560 (1991)). Several outer membrane protein (OMP) genes have been identified and sequenced (Langford et al.,  J. Gen. Microbiol.  138:155-159-(1992)). The lipoligosaccharide (LOS) component of the outer membrane and the genes of its synthetic pathway are under intensive study (Weiser et al.,  J. Bacteriol.  172:3304-3309 (1990)). While a vaccine has been available since 1984, the study of outer membrane components is motivated to some extent by the need for improved vaccines. Recently, the catalase gene was characterized and sequenced as a possible virulence-related gene (Bishni et al., in press). Elucidation of the  H. influenzae  genome will enhance the understanding of how  H. influenzae  causes invasive disease and how best to combat infection.  
       H. influenzae  possesses a highly efficient natural DNA transformation system which has been intensively studied in the non-encapsulated (R), serotype d strain (Kahn and Smith,  J. Membrane Biology  81:89-103 (1984)). At least 16 transformation-specific genes have been identified and sequenced. Of these, four are regulatory (Redfield,  J. Bacteriol.  173:5612-5618 (1991), and Chandler,  Proc.    
      Natl. Acad. Sci. USA 89:1626-1630 (1992)), at least two are involved in recombination processes (Barouki and Smith,  J. Bacterol.  163(2):629-634 (1985)), and at least seven are targeted to the membranes and periplasmic space (Tomb et al.,  Gene  104:1-10 (1991), and Tomb,  Proc. Natl. Acad. Sci. USA  89:10252-10256 (1992)), where they appear to function as structural components or in the assembly of the DNA transport machinery.  H. influenzae  Rd transformation shows a number of interesting features including sequence-specific DNA uptake, rapid uptake of several double-stranded DNA molecules per competent cell into a membrane compartment called the transformasome, linear translocation of a single strand of the donor DNA into the cytoplasm, and synapsis and recombination of the strand with the chromosome by a single-strand displacement mechanism. The  H. influenzae  Rd transformation system is the most thoroughly studied of the gram-negative systems and distinct in a number of ways from the gram-positive systems.  
      The size of  H. influenzae  Rd genome has been determined by pulsed-field agarose gel electrophoresis of restriction digests to be approximately 1.9 Mb, making its genome approximately 40% the size of  E. coli  (Lee and Smith,  J. Bacteriol.  170:4402-4405 (1988)). The restriction map of  H. influenzae  is circular (Lee et al.,  J. Bacteriol.  171:3016-3024 (1989), and Redfield and Lee, “ Haemophilus influenzae  Rd”, pp. 2110-2112, In O&#39;Brien, S. J. (ed), Genetic Maps: Locus Maps of Complex Genomes, Cold Spring Harbor Press, New York). Various genes have been mapped to restriction fragments by Southern hybridization probing of restriction digest DNA bands. This map will be valuable in verification of the assembly of a complete genome sequence from randomly sequenced fragments. GenBank currently contains about 100 kb of non-redundant  H. influenzae  DNA sequences. About half are from serotype b and half from Rd.  
     SUMMARY OF THE INVENTION  
      The present invention is based on the sequencing of the  Haemophilus influenzae  Rd genome. The primary nucleotide sequence which was generated is provided in SEQ ID NO:1.  
      The present invention provides the generated nucleotide sequence of the  Haemophilus influenzae  Rd genome, or a representative fragment thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan. In one embodiment, present invention is provided as a contiguous string of primary sequence information corresponding to the nucleotide sequence depicted in SEQ ID NO:1.  
      The present invention further provides nucleotide sequences which are at least 99.9% identical to the nucleotide sequence of SEQ ID NO:1.  
      The nucleotide sequence of SEQ ID NO:1, a representative fragment thereof, or a nucleotide sequence which is at least 99.9% identical to the nucleotide sequence of SEQ ID NO:1 may be provided in a variety of mediums to facilitate its use. In one application of this embodiment, the sequences of the present invention are recorded on computer readable media. Such media includes, but is not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.  
      The present invention further provides systems, particularly computer-based systems which contain the sequence information herein described stored in a data storage means. Such systems are designed to identify commercially important fragments of the  Haemophilus influenzae  Rd genome.  
      Another embodiment of the present invention is directed to isolated fragments of the  Haemophilus influenzae  Rd genome. The fragments of the  Haemophilus influenzae  Rd genome of the present invention include, but are not limited to, fragments which encode peptides, hereinafter open reading frames (ORFs), fragments which modulate the expression of an operably linked ORF, hereinafter expression modulating fragments (EMFs), fragments which mediate the uptake of a linked DNA fragment into a cell, hereinafter uptake modulating fragments (UMFs), and fragments which can be used to diagnose the presence of  Haemophilus influenzae  Rd in a sample, hereinafter, diagnostic fragments (DFs).  
      Each of the ORF fragments of the  Haemophilus influenzae  Rd genome disclosed in Tables 1(a) and 2, and the EMF found 5′ to the ORF, can be used in numerous ways as polynucleotide reagents. The sequences can be used as diagnostic probes or diagnostic amplification primers for the presence of a specific microbe in a sample, for the production of commercially important pharmaceutical agents, and to selectively control gene expression.  
      The present invention further includes recombinant constructs comprising one or more fragments of the  Haemophilus influenzae  Rd genome of the present invention. The recombinant constructs of the present invention comprise vectors, such as a plasmid or viral vector, into which a fragment of the  Haemophilus influenzae  Rd has been inserted.  
      The present invention further provides host cells containing any one of the isolated fragments of the  Haemophilus influenzae  Rd genome of the present invention. The host cells can be a higher eukaryotic host such as a mammalian cell, a lower eukaryotic cell such as a yeast cell, or can be a procaryotic cell such as a bacterial cell.  
      The present invention is further directed to isolated proteins encoded by the ORFs of the present invention. A variety of methodologies known in the art can be utilized to obtain any one of the proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. In an alternative method, the protein is purified from bacterial cells which naturally produce the protein. Lastly, the proteins of the present invention can alternatively be purified from cells which have been altered to express the desired protein.  
      The invention further provides methods of obtaining homologs of the fragments of the  Haemophilus influenzae  Rd genome of the present invention and homologs of the proteins encoded by the ORFs of the present invention. Specifically, by using the nucleotide and amino acid sequences disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.  
      The invention further provides antibodies which selectively bind one of the proteins of the present invention. Such antibodies include both monoclonal and polyclonal antibodies.  
      The invention further provides hybridomas which produce the above-described antibodies. A hybridoma, is an immortalized cell line which is capable of secreting a specific monoclonal antibody.  
      The present invention further provides methods of identifying test samples derived from cells which express one of the ORF of the present invention or homolog thereof. Such methods comprise incubating a test sample with one or more of the antibodies of the present invention, or one or more of the DFs of the present invention, under conditions which allow a skilled artisan to determine if the sample contains the ORF or product produced therefrom.  
      In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the above-described assays.  
      Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the antibodies, or one of the DFs of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting-presence of bound antibodies or hybridized DFs.  
      Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents capable of binding to a protein encoded by one of the ORFs of the present invention. Specifically, such agents include antibodies (described above), peptides, carbohydrates, pharmaceutical agents and the like. Such methods comprise the steps of: 
          (a) contacting an agent with an isolated protein encoded by one of the ORFs of the present invention; and     (b) determining whether the agent binds to said protein.        

      The complete genomic sequence of  H. influenzae  will be of great value to all laboratories working with this organism and for a variety of commercial purposes. Many fragments of the  Haemophilus influenzae  Rd genome will be immediately identified by similarity searches against GenBank or protein databases and will be of immediate value to  Haemophilus  researchers and for immediate commercial value for the production of proteins or to control gene expression. A specific example concerns PHA synthase. It has been reported that polyhydroxybutyrate is present in the membranes of  H. influenzae  Rd and that the amount correlates with the level of competence for transformation. The PHA synthase that synthesizes this polymer has been identified and sequenced in a number of bacteria, none of which are evolutionarily close to  H. influenzae . This gene has yet to be isolated from  H. influenzae  by use of hybridization probes or PCR techniques. However, the genomic sequence of the present invention allows the identification of the gene by utilizing search means described below.  
      Developing the methodology and technology for elucidating the entire genomic sequence of bacterial and other small genomes has and will greatly enhance the ability to analyze and understand chromosomal organization. In particular, sequenced genomes will provide the models for developing tools for the analysis of chromosome structure and function, including the ability to identify genes within large segments of genomic DNA, the structure, position, and spacing of regulatory elements, the identification of genes with potential industrial applications, and the ability to do comparative genomic and molecular phylogeny. 
    
    
     DESCRIPTION OF THE FIGURES  
       FIG. 1 —restriction map of the  Haemophilus influenzae  Rd genome.  
       FIG. 2 —Block diagram of a computer system  102  that can be used to implement the computer-based systems of present invention.  
       FIG. 3 —A comparison of experimental coverage of up to approximately 4000 random sequence fragments assembled with AutoAssembler (squares) as compared to Lander-Waterman prediction for a 2.5 Mb genome (triangles) and a 1.6 Mb genome (circles) with a 460 bp average sequence length and a 25 bp overlap.  
       FIG. 4 —Data flow and computer programs used to manage, assemble, edit, and annotate the  H. influenzae  genome. Both Macintosh and Unix platforms are used to handle the AB 373 sequence data files (Kerlavage et al.,  Proceedings of the Twenty - Sixth Annual Hawaii International Conference on System Sciences , IEEE Computer Society Press, Washington D.C., 585 (1993)). Factura (AB) is a Macintosh program designed for automatic vector sequence removal and end trimming of sequence files. The program esp runs on a Macintosh platform and parses the feature data extracted from the sequence files by Factura to the Unix based  H. influenzae  relational database. Assembly is accomplished by retrieving a specific set of sequence files and their associated features using stp, an X-windows graphical interface and control program which can retrieve sequences from the  H. influenzae  database using user-defined or standard SQL queries. The sequence files were assembled using TIGR Assembler, an assembly engine designed at TIGR for rapid and accurate assembly of thousands of sequence fragments. TIGR Editor is a graphical interface which can parse the aligned sequence files from TIGR Assembler output and display the alignment and associated electropherograms for contig editing. Identification of putative coding regions was performed with Genemark (Borodovsky and McIninch,  Computers Chem.  17(2):123 (1993)), a Markov and Bayes modeled program for predicting gene locations, and trained on a  H. influenzae  sequence data set. Peptide searches were performed against the three reading frames of each Genemark predicted coding region using blaze (Brutlag et al.,  Computers Chem.  17:203 (1993)) run on a Maspar MP-2 massively parallel computer with 4096 microprocessors. Results from each frame were combined into a single output file by mblzt. Optimal protein alignments were obtained using the program praze which extends alignments across potential frameshifts. The output was inspected using a custom graphic viewing program, gbyob, that interacts directly with the  H. influenzae  database. The alignments were further used to identify potential frameshift errors and were targeted for additional editing.  
       FIG. 5 —A circular representation of the  H. influenzae  Rd chromosome illustrating the location of each predicted coding region containing a database match as well as selected global features of the genome. Outer perimeter: The location of the unique NotI restriction site (designated as nucleotide 1), the RsrII sites, and the SmaI sites. Outer concentric circle: The location of each identified coding region for which a gene identification was made. Each coding region location is coded as to role according to the color code in  FIG. 6 . Second concentric circle: Regions of high G/C content (&gt;42%, red; &gt;40%, blue) and high A/T content (&gt;66%, black; &gt;64%, green). High G/C content regions are specifically associated with the 6 ribosomal operons and the mu-like prophage. Third concentric circle: Coverage by lambda clones (blue). Over 300 lambda clones were sequenced from each end to confirm the overall structure of the genome and identify the 6 ribosomal operons. Fourth concentric circle: The locations of the 6 ribosomal operons (green), the tRNAs (black) and the cryptic mu-like prophage (blue). Fifth concentric circle: Simple tandem repeats. The locations of the following repeats are shown: CTGGCT, GTCT, ATT, AATGGC, TTGA, TTGG, TTTA, TTATC, TGAC, TCGTC, AACC, TTGC, CAAT, CCAA. The putative origin of replication is illustrated by the outward pointing arrows (green) originating near base 603,000. Two potential termination sequences are shown near the opposite midpoint of the circle (red).  
      FIGS.  6 (A)- 6 (D)—Complete map of the  H. influenzae  Rd genome. Predicted coding regions are shown on each strand. rRNA and tRNA genes are shown as lines and triangles, respectively. Genes are color-coded by role category as described in the legend. GeneID numbers correspond to those in Tables 1(a), 1(b) and 2. Where possible, three-letter designations are also provided.  
       FIG. 7 —A comparison of the region of the  H. influenzae  chromosome containing the 8 genes of the fimbrial gene cluster present in  H. influenzae  type b and the same region in  H. influenzae  Rd. The region is flanked by the pepN and purE genes in both organisms. However in the non-infectious Rd strain the 8 genes of the fimbrial gene cluster have been excised. A 172 bp spacer region is located in this region in the Rd strain and continues to be flanked by the pepN and purE genes.  
       FIG. 8 —Hydrophobicity analysis of five predicted channel-proteins. The amino acid sequences of five predicted coding regions that do not display homology with known peptide sequences (GenBank release 87), each exhibit multiple hydrophobic domains that are characteristic of channel-forming proteins. The predicted coding region sequences were analyzed by the Kyte-Doolittle algorithm (Kyte and Doolittle,  J. Mol. Biol.  157:105 (1982)) (with a range of 11 residues) using the GeneWorks software package (Intelligenetics). 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
      The present invention is based on the sequencing of the  Haemophilus influenzae  Rd genome. The primary nucleotide sequence which was generated is provided in SEQ ID NO:1. As used herein, the “primary sequence” refers to the nucleotide sequence represented by the IUPAC nomenclature system.  
      The sequence provided in SEQ ID NO:1 is oriented relative to a unique Not I restriction endonuclease site found in the  Haemophilus influenzae  Rd genome. A skilled artisan will readily recognize that this start/stop point was chosen for convenience and does not reflect a structural significance.  
      The present invention provides the nucleotide sequence of SEQ ID NO:1, or a representative fragment thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan. In one embodiment, the sequence is provided as a contiguous string of primary sequence information corresponding to the nucleotide sequence provided in SEQ ID NO:1.  
      As used herein, a “representative fragment of the nucleotide sequence depicted in SEQ ID NO:1” refers to any portion of SEQ ID NO:1 which is not presently represented within a publicly available database. Preferred representative fragments of the present invention are  Haemophilus influenzae  open reading frames, expression modulating fragments, uptake modulating fragments, and fragments which can be used to diagnose the presence of  Haemophilus influenzae  Rd in sample. A non-limiting identification of such preferred representative fragments is provided in Tables 1(a) and and 2.  
      The nucleotide sequence information provided in SEQ ID NO:1 was obtained by sequencing the  Haemophilus influenzae  Rd genome using a megabase shotgun sequencing method. Using three parameters of accuracy discussed in the Examples below, the present inventors have calculated that the sequence in SEQ ID NO:1 has a maximum accuracy of 99.98%. Thus, the nucleotide sequence provided in SEQ ID NO:1 is a highly accurate, although not necessarily a 100% perfect, representation of the nucleotide sequence of the  Haemophilus influenzae  Rd genome.  
      As discussed in detail below, using the information provided in SEQ ID NO:1 and in Tables 1(a) and 2 together with routine cloning and sequencing methods, one of ordinary skill in the art will be able to clone and sequence all “representative fragments” of interest including open reading frames (ORFs) encoding a large variety of  Haemophilus influenzae  proteins. In very rare instances, this may reveal a nucleotide sequence error present in the nucleotide sequence disclosed in SEQ ID NO:1. Thus, once the present invention is made available (i.e., once the information in SEQ ID NO:1 and Tables 1(a) and 2 have been made available), resolving a rare sequencing error in SEQ ID NO:1 will be well within the skill of the art. Nucleotide sequence editing software is publicly available. For example, Applied Biosystem&#39;s (AB) AutoAssembler™ can be used as an aid during visual inspection of nucleotide sequences.  
      Even if all of the very rare sequencing errors in SEQ ID NO:1 were corrected, the resulting nucleotide sequence would still be at least 99.9% identical to the nucleotide sequence in SEQ ID NO:1.  
      The nucleotide sequences of the genomes from different strains of  Haemophilus influenzae  differ slightly. However, the nucleotide sequence of the genomes of all  Haemophilus influenzae  strains will be at least 99.9% identical to the nucleotide sequence provided in SEQ ID NO:1.  
      Thus, the present invention further provides nucleotide sequences which are at least 99.9% identical to the nucleotide sequence of SEQ ID NO:1 in a form which can be readily used, analyzed and interpreted by the skilled artisan. Methods for determining whether a nucleotide sequence is at least 99.9% identical to the nucleotide sequence of SEQ ID NO:1 are routine and readily available to the skilled artisan. For example, the well known fasta algothrithm (Pearson and Lipman,  Proc. Natl. Acad. Sci. USA  85:2444 (1988)) can be used to generate the percent identity of nucleotide sequences.  
     Computer Related Embodiments  
      The nucleotide sequence provided in SEQ ID NO:1, a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ ID NO:1 may be “provided” in a variety of mediums to facilitate use thereof. As used herein, provided refers to a manufacture, other than an isolated nucleic acid molecule, which contains a nucleotide sequence of the present invention, i.e., the nucleotide sequence provided in SEQ ID NO:1, a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ ID NO:1. Such a manufacture provides the  Haemophilus influenzae  Rd genome or a subset thereof (e.g., a  Haemophilus Influenzae  Rd open reading frame (ORF)) in a form which allows a skilled artisan to examine the manufacture using means not directly applicable to examining the  Haemophilus influenzae  Rd genome or a subset thereof as it exists in nature or in purified form.  
      In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, “computer readable media” refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the present invention.  
      As used herein, “recorded” refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently know methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information of the present invention.  
      A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and MicroSoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of dataprocessor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention.  
      By providing the nucleotide sequence of SEQ ID NO:1, a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ ID NO:1 in computer readable form, a skilled artisan can routinely access the sequence information for a variety of purposes. Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium., The examples which follow demonstrate how software which implements the BLAST (Altschul et al.,  J. Mol. Biol.  215:403-410 (1990)) and BLAZE (Brutlag et al.,  Comp. Chem.  17:203-207 (1993)) search algorithms on a Sybase system was used to identify open reading frames (ORFs) within the  Haemophilus influenzae  Rd genome which contain homology to ORFs or proteins from other organisms. Such ORFs, are protein encoding fragments within the  Haemophilus influenzae  Rd genome and are useful in producing commercially important proteins such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.  
      The present invention further provides systems, particularly computer-based systems, which contain the sequence information described herein. Such systems are designed to identify commercially important fragments of the  Haemophilus influenzae  Rd genome.  
      As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based system are suitable for use in the present invention.  
      As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means. As used herein, “data storage means” refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.  
      As used herein, “search means” refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of the  Haemophilus influenzae  Rd genome which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. Examples of such software includes, but is not limited to, MacPattern (EMBL), BLASTN and BLASTX (NCBIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems.  
      As used herein, a “target sequence” can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues. However, it is well recognized that searches for commercially important fragments of the  Haemophilus influenzae  Rd genome, such as sequence fragments involved in gene expression and protein processing, may be of shorter length.  
      As used herein, “a target structural motif,” or “target motif,” refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzymic active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).  
      A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. A preferred format for an output means ranks fragments of the  Haemophilus influenzae  Rd genome possessing varying degrees of homology to the target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences which contain various amounts of the target sequence or target motif and identifies the degree of homology contained in the identified fragment.  
      A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the  Haemophilus influenzae  Rd genome. In the present examples, implementing software which implement the BLAST and BLAZE algorithms (Altschul et al.,  J. Mol. Biol.  215:403-410. (1990)) was used to identify open reading frames within the  Haemophilus influenzae  Rd genome. A skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer-based systems of the present invention.  
      One application of this embodiment is provided in  FIG. 2 .  FIG. 2  provides a block diagram of a computer system  102  that can be used to implement the present invention. The computer system  102  includes a processor  106  connected to a bus  104 . Also connected to the bus  104  are a main memory  108  (preferably implemented as random access memory, RAM) and a variety of secondary storage devices  110 , such as a hard drive  112  and a removable medium storage device  114 . The removable medium storage device  114  may represent, for example, a floppy disk drive, a CD-ROM drive, a magnetic tape drive, etc. A removable storage medium  116 . (such as a floppy disk, a compact disk, a magnetic tape, etc.) containing control logic and/or data recorded therein may be inserted into the removable medium storage device  114 . The computer system  102  includes appropriate software for reading, the control logic and/or the data from the removable medium storage device  114  once inserted in the removable medium storage device  114 .  
      A nucleotide sequence of the present invention may be stored in a well known manner in the main memory  108 , any of the secondary storage devices  110 , and/or a removable storage medium  116 . Software for accessing and processing the genomic sequence (such as search tools, comparing tools, etc.) reside in main memory  108  during execution.  
     Biochemical Embodiments  
      Another embodiment of the present invention is directed to isolated fragments of the  Haemophilus influenzae  Rd genome. The fragments of the  Haemophilus influenzae  Rd genome of the present invention include, but are not limited to fragments which encode peptides, hereinafter open reading frames (ORFs), fragments which modulate the expression of an operably linked ORF hereinafter expression modulating fragments (EMFs), fragments which mediate the uptake of a linked DNA fragment into a cell, hereinafter uptake modulating fragments (UMFs), and fragments which can be used to diagnose the presence of  Haemophilus influenzae  Rd in a sample, hereinafter diagnostic fragments (DFs).  
      As used herein, an “isolated nucleic acid molecule” or an “isolated fragment of the  Haemophilus influenzae  Rd genome” refers to a nucleic acid molecule possessing a specific nucleotide sequence which has been subjected to purification means to reduce, from the composition, the number of compounds which are normally associated with the composition. A variety of purification means can be used to generated the isolated fragments of the present invention. These include, but are not limited to methods which separate constituents of a solution based on charge, solubility, or size.  
      In one embodiment,  Haemophilus  influenaze Rd DNA can be mechanically sheared to produce fragments of 15-20 kb in length. These fragments can then be used to generate an  Haemophilus influenzae  Rd library by inserting them into labda clones as described in the Examples below. Primers flanking, for example, an ORF provided in Table 1(a) can then be generated using nucleotide sequence information provided in SEQ ID NO:1. PCR cloning can then be used to isolate the ORF from the lambda DNA library. PCR cloning is well known in the art. Thus, given the availability of SEQ ID NO:1, Table 1(a) and Table 2, it would be routine to isolate any ORF or other nucleic acid fragment of the present invention.  
      The isolated nucleic acid molecules of the present invention include, but are not limited to single stranded and double stranded DNA, and single stranded RNA.  
      As used herein, an “open reading frame,” ORF, means a series of triplets coding for amino acids without any termination codons and is a sequence translatable-into protein. Tables 1a, 1b and 2 identify ORFs—in the  Haemophilus influenzae  Rd genome. In particular, Table 1a indicates the location of ORFs within the  Haemophilus influenzae  genome which encode the recited protein based on homology matching with protein sequences from the organism appearing in parentheticals (see the fourth column of Table 1(a)).  
      The first column of Table 1 (a) provides the “GeneID” of a particular ORF. This information is useful for two reasons. First, the complete map of the  Haemophilus influenzae  Rd genome provided in FIGS.  6 (A)- 6 (D) refers to the ORFs according to their GeneID numbers. Second, Table 1(b) uses the GeneID numbers to indicate which ORFs were provided previously in a public database.  
      The second and third columns in Table 1(a) indicate an ORFs position in the nucleotide sequence provided in SEQ ID NO:1. One of ordinary skill will recognize that ORFs may be oriented in opposite directions in the  Haemophilus influenae  genome. This is reflected in columns 2 and 3.  
      The fifth column of Table 1(a) indicates the percent identity of the protein encoded for by an ORF to the corresponding protein from the organism appearing in parentheticals in the fourth column.  
      The sixth column of Table 1(a) indicates the percent similarity of the protein encoded for by an ORF to the corresponding protein from the organism appearing in parentheticals in the fourth column. The concepts of percent identity and percent similarity of two-polypeptide sequences is well understood in the art. For example, two polypeptides 10 amino acids in length which differ at three amino acid positions (e.g., at positions 1, 3 and 5) are said to have a percent identity of 70%. However, the same two polypeptides would be deemed to have a percent similarity of 80% if, for example at position 5, the amino acids moieties, although not identical, were “similar” (i.e., possessed similar biochemical characteristics).  
      The seventh column in Table 1(a) indicates the lenth of the amino acid homology match.  
      Table 2 provides ORFs of the  Haemophilus influenzae  Rd genome which encode polypeptide sequences which did not elicit a “homology match” with a known protein sequence from another organism. Further details concerning the algorithms and criteria used for homology searches are provided in the Examples below.  
      A skilled artisan can readily identify ORFs in the  Haemophilus influenzae  Rd genome other than those listed in Tables 1(a), 1(b) and 2, such as ORFs which are overlapping or encoded by the opposite strand of an identified ORF in addition to those ascertainable using the computer-based systems of the present invention.  
      As used herein, an “expression modulating fragment,” EMF, means a series of nucleotide molecules which modulates the expression of an operably linked ORF or EMF.  
      As used herein, a sequence is said to “modulate the expression of an operably linked sequence” when the expression of the sequence is altered by the presence of the EMF. EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are fragments which induce the expression or an operably linked ORF in response to a specific regulatory factor or physiological event. A review of known EMFs from  Haemophilus  are described by (Tomb et al.  Gene  104:1-10 (1991), Chandler, M. S., Proc. Natl. Acad. Sci. USA 89:1626-1630 (1992).  
      EMF sequences can be identified within the  Haemophilus influenzae  Rd genome by their proximity to the ORFs provided in Tables 1(a), 1(b) and 2. An intergenic segment, or a fragment of the intergenic segment, from about 10 to 200 nucleotides in length, taken 5′ from any one of the ORFs of Tables 1(a), 1(b), or 2 will modulate the expression of an operably linked 3′ ORF in a fashion similar to that found with the naturally linked ORF sequence. As used herein, an “intergenic segment” refers to the fragments of the  Haemophilus  genome which are between two ORF(s) herein described. Alternatively, EMFs can be identified using known EMFs as a target sequence or target motif in the computer-based systems of the present invention.  
      The presence and activity of an EMF can be confirmed using an EMF trap vector. An EMF trap vector contains a cloning site 5′ to a marker sequence. A marker sequence encodes an identifiable phenotype, such as antibiotic resistance or a complementing nutrition auxotrophic factor, which can be identified or assayed when the EMF trap vector is placed within an appropriate host under appropriate conditions. As described above, a EMF will modulate the expression of an operably linked marker sequence. A more detailed discussion of various marker sequences is provided below.  
      A sequence which is suspected as being a EMF is cloned in all three reading frames in one or more restriction sites upstream from the marker sequence in the EMF trap vector. The vector is then transformed into an appropriate host using known procedures and the phenotype of the transformed host in examined under appropriate conditions. As described above, an EMF will modulate the expression of an operably linked marker sequence.  
      As used herein, an “uptake modulating fragment,” UMF, means a series of nucleotide molecules which mediate the uptake of a linked DNA fragment into a cell. UMFs can be readily identified using known UMFs as a target sequence or target motif with the computer-based systems described above.  
      The presence and activity of a UMF can be confirmed by attaching the suspected UMF to a marker sequence. The resulting nucleic acid molecule is then incubated with an appropriate host under appropriate conditions and the uptake of the marker sequence is determined. As described above, a UMF will increase the frequency of uptake of a linked marker sequence. A review of DNA uptake in  Haemophilus  is provided by Goodgall, S. H., et al.,  J. Bact.  172:5924-5928 (1990).  
      As used herein, a “diagnostic fragment,” DF, means a series of nucleotide molecules which selectively hybridize to  Haemophilus influenzae  sequences. DFs can be readily identified by identifying unique sequences within the  Haemophilus influenzae  Rd genome, or by generating and testing probes or amplification primers consisting of the DF sequence in an appropriate diagnostic format which determines amplification or hybridization selectivity.  
      The sequences falling within the scope of the present invention are not limited to the specific sequences herein described, but also include allelic and species variations thereof. Allelic and species variations can be routinely determined by comparing the sequence provided in SEQ ID NO:1, a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ ID NO:1 with a sequence from another isolate of the same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon for another which encodes the same amino acid is expressly contemplated.  
      Any specific sequence disclosed herein can be readily screened for errors by resequencing a particular fragment, such as an ORF, in both directions (i.e., sequence both strands). Alternatively, error screening can be performed by sequencing corresponding polynucleotides of  Haemophilus influenzae  origin isolated by using part or all of the fragments in question as a probe or primer.  
      Each of the ORFs of the  Haemophilus influenzae  Rd genome disclosed in Tables 1(a), 1(b) and 2, and the EMF found 5′ to the ORF, can be used in numerous ways as polynucleotide reagents. The sequences can be used as diagnostic probes or diagnostic amplification primers to detect the presence of a specific microbe, such as  Haemophilus influenzae  RD, in a sample. This is especially the case with the fragments or ORFs of Table 2, which will be highly selective for  Haemophilus influenzae.    
      In addition, the fragments of the present invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA. Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription (triple helix—see Lee et al.,  Nucl. Acids Res.  6:3073 (1979); Cooney et al.,  Science  241:456 (1988); and Dervan et al.,  Science  251:1360 (1991)) or to the mRNA itself (antiserise—Okano,  J. Neurochem.  56:560 (1991);  Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression , CRC Press, Boca Raton, Fla. (1988)). Triple helix—formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide.  
      The present invention further provides recombinant constructs comprising one or more fragments of the  Haemophilus influenzae  Rd genome of the present invention. The recombinant constructs of the present invention comprise a vector, such as a plasmid or viral vector, into which a fragment of the  Haemophilus influenzae  Rd has been inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs of the present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. For vectors comprising the EMFs and UMFs of the present invention, the vector may further comprise a marker sequence or heterologous ORF operably linked to the EMF or UMF. Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs of the present invention. The following vectors are provided by way of example. Bacterial: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia). Eukaryotic: pWLneo, pSV2cat, pOG44, pXT1, pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL (Pharmacia).  
      Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lacI, lacZ, T3, T7, gpt, lambda P R , and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late, SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.  
      The present invention further provides host cells containing any one of the isolated fragments of the  Haemophilus influenzae  Rd genome of the present invention, wherein the fragment has been introduced into the host cell using known transformulation methods. The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or the host cell can be a procaryotic cell, such as a bacterial cell. Introduction of the recombinant construct into the host cell can be effected by calcium phosphate transfection, DEAE, dextran mediated transfection, or electroporation (Davis, L. et al.,  Basic Methods in Molecular Biology  (1986)).  
      The host cells containing one of the fragments of the  Haemophilus influenzae  Rd genome of the present invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to produce a heterologous protein under the control of the EMF.  
      The present invention further provides isolated polypeptides encoded by the nucleic acid fragments of the present invention or by degenerate variants of the nucleic acid fragments of the present invention. By “degenerate variant” is intended nucleotide fragments which differ from a nucleic acid fragment of the present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy of the Genetic Code, encode an identical polypeptide sequence. Preferred nucleic acid fragments of the present invention are the ORFs depicted in Table 1(a) which encode proteins.  
      A variety of methodologies known in the art can be utilized to obtain any one of the isolated polypeptides or proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. Fragments are useful, for example, in generating antibodies against the native polypeptide. In an alternative method, the polypeptide or protein is purified from bacterial cells which naturally produce the polypeptide or protein. One skilled in the art can readily follow known methods for isolating polpeptides and proteins in order to obtain one of the isolated polypeptides or proteins of the present invention. These include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography.  
      The polypeptides and proteins of the present invention can alternatively be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. One skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one of the polypeptides or proteins of the present invention.  
      Any host/vector system can be used to express one or more of the ORFs of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, Cv-1 cell, COS cells, and Sf9 cells, as well as prokaryotic host such as  E. coli  and  B. subtilis . The most preferred cells are those which do not normally express the particular polypeptide or protein or which expresses the polypeptide or protein at low natural level.  
      “Recombinant,” as used herein, means that a polypeptide or protein is derived from recombinant (e.g., microbial or mammalian) expression systems. “Microbial” refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, “recombinant microbial” defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g.,  E. coli , will be free of glycosylation modifications; polypeptides or proteins expressed in yeast will have a glycosylation pattern different from that expressed in mammalian cells.  
      “Nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. Generally, DNA segments encoding the polypeptides and proteins provided by this invention are assembled from fragments of the  Haemophilus influenzae  Rd genome and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.  
      “Recombinant expression vehicle or vector” refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. The expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription initiation and termination sequences. Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an N-terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.  
      “Recombinant expression system” means host cells which have stably integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extra chromosomally. The cells can be prokaryotic or eukaryotic. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction of the regulatory elements linked to the DNA segment or synthetic gene to be expressed.  
      Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryatic and eukaryotic hosts are described by Sambrook, et al., in  Molecular Cloning: A Laboratory Manual , Second Edition, Cold Spring Harbor, N.Y. (1989), the disclosure of which is hereby incorporated by reference.  
      Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of  E. coli  and  S. cerevisiae  TRP1 gene, and a promoter derived from a highly-expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), a-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product.  
      Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector and to, if desirable, provide amplification within the host. Suitable prokaryotic hosts for transformation include  E. coli Bacillus subtilis, Salmonella typhimunium  and various species within the genera  Pseudomonas, Streptomyces , and  Staphylococcus , although others may, also be employed as a matter of choice.  
      As a representative but nonlimiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pKK223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (Promega Biotec, Madison, Wis., USA). These pBR322 “backbone” sections are combined with an appropriate promoter and the structural sequence to be expressed.  
      Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter is derepressed by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification.  
      Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman,  Cell  23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines. Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.  
      Recombinant polypeptides and proteins produced in bacterial culture is usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents.  
      The present invention further includes isolated polypeptides, proteins and nucleic acid molecules which are substantially equivalent to those herein described. As used herein, substantially equivalent can refer both to nucleic acid and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between reference and subject sequences. For purposes of the present invention, sequences having equivalent biological activity, and equivalent expression characteristics are considered substantially equivalent. For purposes of determining equivalence, truncation of the mature sequence should be disregarded.  
      The invention further provides methods of obtaining homologs from other strains of  Haemophilus influenzae , of the fragments of the  Haemophilus influenzae  Rd genome of the present-invention and homologs of the proteins encoded by the ORFs of the present invention. As used herein, a sequence or protein of  Haemophilus influenzae  is defined as a homolog of a fragment of the  Haemophilus influenzae  Rd genome or a protein encoded by one of the ORFs of the present invention, if it shares significant homology to one of the fragments of the  Haemophilus influenzae  Rd genome of the present invention or a protein encoded by one of the ORFs of the present invention. Specifically, by using the sequence disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.  
      As used herein, two nucleic acid molecules or proteins are said to “share significant homology” if the two contain regions which process greater than 85% sequence (amino acid or nucleic acid) homology.  
      Region specific primers or probes derived from the nucleotide sequence provided in SEQ ID NO:1 or from a nucleotide sequence at least 99.9% identical to SEQ ID NO:1 can be used to prime DNA synthesis and PCR amplification, as well as to identify colonies containing cloned DNA encoding a homolog using known methods (Innis et al.,  PCR Protocols , Academic Press, San Diego, Calif. (1990)).  
      When using primers derived from SEQ ID NO:1 or from a nucleotide sequence at least 99.9% identical to SEQ ID NO:1, one skilled in the art will recognize that by employing high stringency conditions (e.g., annealing at 50-60° C.) only sequences which are greater than 75% homologous to the primer will be amplified. By employing lower stringency conditions (e.g., annealing at 35-37° C.), sequences which are greater than 40-50% homologous to the primer will also be amplified.  
      When using DNA probes derived from SEQ ID NO:1 or from a nucleotide sequence at least 99.9% identical to SEQ ID NO:1 for colony/plaque hybridization, one skilled in the art will recognize that by employing high stringency conditions (e.g., hybridizing at 50-65° C. in 5×SSPC and 50% formamide, and washing at 50-65° C. in 0.5×SSPC), sequences having regions which are greater than 90% homologous to the probe can be obtained, and that by employing lower stringency conditions (e.g., hybridizing at 35-37° C. in 5×SSPC and 40-45% formamide, and washing at 42° C. in SSPC), sequences having regions which are greater than 35-45% homologous to the probe will be obtained.  
      Any organism can be used as the source for homologs of the present invention so long as the organism naturally expresses such a protein or contains genes encoding the same. The most preferred organism for isolating homologs are bacterias which are closely related to  Haemophilus influenzae  Rd.  
      Uses for the Compositions of the Invention  
      Each ORF provided in Table 1(a) was assigned to one of  102  biological role categories adapted from Riley,  M., Microbiology Reviews  57(4):862 (1993)). This allows the skilled artisan to determine a use for each identified coding sequence. Tables 1 (a) further provides an identification of the type of polypeptide which is encoded for by each ORF. As a result, one skilled in the art can use the polypeptides of the present invention for commercial, therapeutic and industrial purposes consistent with the type of putative identification of the polypeptide.  
      Such identifications permit one skilled in the art to use the  Haemophilus influenzae  ORFs in a manner similar to the known type of sequences for which the identification is made, for example, to ferment a particular sugar source or to produce a particular metabolite. (For a review of enzymes used within the commercial industry, see  Biochemical Engineering and Biotechnology Handbook  2nd, eds. Macmillan Publ. Ltd., NY (1991) and Biocatalysts in Organic Syntheses, ed. J. Tramper et al., Elsevier Science Publishers, Amsterdam, The Netherlands (1985)).  
      1. Biosynthetic Enzymes  
      Open reading frames encoding proteins involved in mediating the catalytic reactions involved in intermediary and macromolecular metabolism, the biosynthesis of small molecules, cellular processes and other functions includes enzymes involved in the degradation of the intermediary products of metabolism, enzymes involved in central intermediary metabolism, enzymes involved in respiration, both aerobic and anaerobic, enzymes involved in fermentation, enzymes involved in ATP proton motor force conversion, enzymes involved in broad regulatory function, enzymes involved in amino acid synthesis, enzymes involved in nucleotide synthesis, enzymes involved in cofactor and vitamin synthesis, can be used for industrial biosynthesis. The various metabolic pathways present in  Haemophilus  can be identified based on absolute nutritional requirements as well as by examining the various enzymes identified in Table 1(a).  
      Identified within the category of intermediary metabolism, a number of the proteins encoded by the identified ORFs in Tables 1(a) are particularly involved in the degradation of intermediary metabolites as well as non-macromolecular metabolism. Some of the enzymes identified include amylases, glucose oxidases, and catalase.  
      Proteolytic enzymes are another class of commercially important enzymes. Proteolytic enzymes find use in a number of industrial processes including the processing of flax and other vegetable fibers, in the extraction, clarification and depectinization of fruit juices, in the extraction of vegetables&#39; oil and in the maceration of fruits and vegetables to give unicellular fruits. A detailed review of the proteolytic enzymes used in the food industry is provided by Rombouts et al.,  Symbiosis  21:79 (1986) and Voragen et al. in  Biocatalyst in Agricultural Biotechnology , edited J. R. Whitaker et al.,  American Chemical Society Symposium Series  389:93 (1989)).  
      The metabolism of glucose, galactose, fructose and xylose are important parts of the primary metabolism of  Haemophilus . Enzymes involved in the degradation of these sugars can be used in industrial fermentation. Some of the important sugar transforming enzymes, from a commercial viewpoint, include sugar isomerases such as glucose isomerase. Other metabolic enzymes have found commercial use such as glucose oxidases which produces ketogulonic acid (KGA). KGA is an intermediate in the commercial production of ascorbic acid using the Reichstein&#39;s procedure (see Krueger et al.,  Biotechnology  6(A), Rhine, H. J. et al., eds., Verlag Press, Weinheim, Germany (1984)).  
      Glucose oxidase (GOD) is commercially available and has been used in purified form as well as in an immobilized form for the deoxygenation of beer. See Hartmeir et al.,  Biotechnology Letters  1:21 (1979). The most important application of GOD is the industrial scale fermentation of gluconic acid. Market for gluconic acids which are used in the detergent, textile, leather, photographic, pharmaceutical, food, feed and concrete industry (see Bigelis in  Gene Manipulations and Fungi , Benett, J. W. et al., eds., Academic Press, New York (1985), p. 357). In addition to industrial applications, GOD has found applications in medicine for quantitative determination of glucose in body fluids recently in biotechnology for analyzing syrups from starch and cellulose hydrosylates. See Owusu et al.,  Biochem. et Biophysica. Acta.  872:83 (1986).  
      The main sweetener used in the world today is sugar which comes from sugar beets and sugar cane. In the field of industrial enzymes, the glucose isomerase process shows the largest expansion in the market today. Initially, soluble enzymes were used and later immobilized enzymes were developed (Krueger et al.,  Biotechnology, The Textbook of Industrial Microbiology , Sinauer Associated Incorporated, Sunderland, Mass. (1990)). Today, the use of glucose-produced high fructose syrups is by far the largest industrial business using immobilized enzymes. A review of the industrial use of these enzymes is provided by Jorgensen,  Starch  40:307 (1988).  
      Proteinases, such as alkaline serine proteinases, are used as detergent additives and thus represent one of the largest volumes of microbial enzymes used in the industrial sector. Because of their industrial importance, there is a large body of published and unpublished information regarding the use of these enzymes in industrial processes. (See Faultman et al.,  Acid Proteases Structure Function and Biology , Tang, J., ed., Plenum Press, New York (1977) and Godfrey et al.,  Industrial Enzymes , MacMillan Publishers, Surrey, UK (1983) and Hepner et al.,  Report Industrial Enzymes by  1990, Hel Hepner &amp; Associates, London (1986)).  
      Another class of commercially usable proteins of the present invention are the microbial lipases identified in Table 1 (see Macrae et al.,  Philosophical Transactions of the Chiral Society of London  310:227 (1985) and Poserke,  Journal of the American Oil Chemist Society  61:1758 (1984). A major use of lipases is in the fat and oil industry for the production of neutral glycerides using lipase catalyzed inter-esterification of readily available triglycerides. Application of lipases include the use as a detergent additive to facilitate the removal of fats from fabrics in the course of the washing procedures.  
      The use of enzymes, and in particular microbial enzymes, as catalyst for key steps in the synthesis of complex organic molecules is gaining popularity at a great rate. One area of great interest is the preparation of chiral intermediates. Preparation of chiral intermediates is of interest to a wide range of synthetic chemists particularly those scientists involved with the preparation of new pharmaceuticals, agrochemicals, fragrances and flavors. (See Davies et al.,  Recent Advances in the Generation of Chiral Intermediates Using Enzymes , CRC Press, Boca Raton, Fla. (1990)). The following reactions catalyzed by enzymes are of interest to organic chemists: hydrolysis of carboxylic acid esters, phosphate esters, amides and nitriles, esterification reactions, trans-esterification reactions, synthesis of amides, reduction of alkanones and oxoalkanates, oxidation of alcohols to carbonyl compounds, oxidation of sulfides to sulfoxides, and carbon bond forming reactions such as the aldol reaction. When considering the use of an enzyme encoded by one of the ORFs of the present invention for biotransformation and organic synthesis it is sometimes necessary to consider the respective advantages and disadvantages of using a microorganism as opposed to an isolated enzyme. Pros and cons of using a whole cell system on the one hand or an isolated partially purified enzyme on the other hand, has been described in detail by Bud et al.,  Chemistry in Britain  (1987), p. 127.  
      Amino transferases, enzymes involved in the biosynthesis and metabolism of amino acids, are useful in the catalytic production of amino acids. The advantages of using microbial based enzyme systems is that the amino transferase enzymes catalyze the stereo-selective synthesis of only l-amino acids and generally possess uniformly high catalytic rates. A description of the use of amino transferases for amino acid production is provided by Roselle-David,  Methods of Enzymology  136:479 (1987).  
      Another category of useful proteins encoded by theORFs of the present invention include enzymes involved in nucleic acid synthesis, repair, and recombination. A variety of commercially important enzymes have previously been isolated from members of  Haemophilus  sp. These include the Hinc II, Hind III, and Hinf I restriction endonucleases. Table 1(a) identifies a wide array of enzymes, such as restriction enzymes, ligases, gyrases and methylases, which have immediate use in the biotechnology industry.  
      2. Generation of Antibodies  
      As described here, the proteins of the present invention, as well as homologs thereof, can be used in a variety procedures and methods known in the art which are, currently applied to other proteins. The proteins of the present invention can further be used to generate an antibody which selectively binds the protein. Such antibodies can be either monoclonal or polyclonal antibodies, as well fragments of these antibodies, and humanized forms.  
      The invention further provides antibodies which selectively bind to one of the proteins of the present invention and hybridomas which produce these antibodies. A hybridoma is an immortalized cell line which is capable of secreting a specific monoclonal antibody.  
      In general, techniques for preparing polyclonal and monoclonal antibodies as well as hybridomas capable of producing the desired antibody are well known in the art (Campbell, A. M.,  Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology , Elsevier Science Publishers, Amsterdam, The Netherlands (1984); St. Groth et al.,  J. Immunol. Methods  35:1-21 (1980); Kohler and Milstein,  Nature  256:495-497 (1975)), the trioma technique, the human B-cell hybridoma technique (Kozbor et al.,  Immunology Today  4:72 (1983); Cole et al., in  Monoclonal Antibodies and Cancer Therapy , Alan R. Liss, Inc. (1985), pp. 77-96).  
      Any animal (mouse, rabbit, etc.) which is known to produce antibodies can be immunized with the pseudogene polypeptide. Methods for immunization are well known in the art. Such methods include subcutaneous or interperitoneal injection of the polypeptide. One skilled in the art will recognize that the amount of the protein encoded by the ORF of the present-invention used for immunization will vary based on the animal which is immunized, the antigenicity of the peptide and the site of injection.  
      The protein which is used as an immunogen may be modified or administered in an adjuvant in order to increase the protein&#39;s antigenicity. Methods of increasing the antigenicity of a protein are well known in the art and include, but are not limited to coupling the antigen with a heterologous protein (such as globulin or β-galactosidase) or through the inclusion of an adjuvant during immunization.  
      For monoclonal antibodies, spleen cells from the immunized animals are removed, fused with myeloma cells, such as SP2/0-Ag14 myeloma cells, and allowed to become monoclonal antibody producing hybridoma cells.  
      Any one of a number of methods well known in the art can be used to identify the hybridoma cell which produces an antibody with the desired characteristics. These include screening the hybridomas with an ELISA assay, western blot analysis, or radioimmunoassay (Lutz et al.,  Exp. Cell Res.  175:109-124 (1988)).  
      Hybridomas secreting the desired antibodies are cloned and the class and subclass is determined using procedures known in the art (Campbell, A. M.,  Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology , Elsevier Science Publishers, Amsterdam, The Netherlands (1984)).  
      Techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778) can be adapted to produce single chain antibodies to proteins of the present invention.  
      For polyclonal antibodies, antibody containing antisera is isolated from the immunized animal and is screened for the presence of antibodies with the desired specificity using one of the above-described procedures.  
      The present invention further provides the above-described antibodies in detectably labelled form. Antibodies can be detectably labelled through the use of radioisotopes, affinity labels (such as biotin, avidin, etc.), enzymatic labels (such as horseradish peroxidase, alkaline phosphatase, etc.) fluorescent labels (such as FITC or rhodamine, etc.), paramagnetic atoms, etc. Procedures for accomplishing such labelling are well-known in the art, for example see (Sternberger, L. A. et al.,  J. Histochem. Cytochem.  18:315 (1970); Bayer, E. A. et al.,  Meth. Enzym.  62:308 (1979); Engval, E. et al.,  Immunol.  109:129 (1972); Goding, J. W.  J. Immunol. Meth.  13:215 (1976)).  
      The labeled antibodies of the present invention can be used for in vitro, in vivo, and in situ assays to identify cells or tissues in which a fragment of the  Haemophilus influenzae  Rd genome is expressed.  
      The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and sepharose, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D. M. et al., “ Handbook of Experimental Immunology”  4th Ed., Blackwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W. D. et al.,  Meth. Enzym.  34 Academic Press, N.Y. (1974)). The immobilized antibodies of the present invention can be used for in vitro, in vivo, and in situ assays as well as for immunoaffinity purification of the proteins of the present invention.  
      3. Diagnostic Assays and Kits  
      The present invention further provides methods to identify the expression of one of the ORFs of the present invention, or homolog thereof, in a test sample, using one of the DFs or antibodies of the present invention.  
      In detail, such methods comprise incubating a test sample with one or more of the antibodies or one or more of the DFs of the present invention and assaying for binding of the DFs or antibodies to components within the test sample.  
      Conditions for incubating a DF or antibody with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the DF or antibody used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the DFs or antibodies of the present invention. Examples of such assays can be found in Chard, T.,  An Introduction to Radioimmunoassay and Related Techniques , Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G. R. et al.,  Techniques in Immunocytochemistry , Academic Press, Orlando, Fla. Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P.,  Practice and Theory of Enzyme Immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology , Elsevier Science Publishers, Amsterdam, The Netherlands (1985).  
      The test samples of the present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized.  
      In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention.  
      Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the DFs or antibodies of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound DF or antibody.  
      In detail, a compartmentalized kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or DF.  
      Types of detection reagents include labelled nucleic acid probes, labelled secondary antibodies, or in the alternative, if the primary antibody is labelled, the enzymatic, or antibody binding reagents which are capable of reacting with the labelled antibody. One skilled in the art will readily recognize that the disclosed DFs and antibodies of the present invention can be readily incorporated into one of the established kit formats which are well known in the art.  
      4. Screening Assay for Binding Agents  
      Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents which bind to a protein encoded by one of the ORFs of the present invention or to one of the fragments and the  Haemophilus  genome herein described.  
      In detail, said method comprises the steps of: 
          (a) contacting an agent with an isolated protein encoded by one of the ORFs of the present invention, or an isolated fragment of the  Haemophilus  genome; and     (b) determining whether the agent binds to said protein or said fragment.        

      The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques.  
      For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF of the present invention.  
      Alternatively, agents may be rationally selected or designed., As used herein, an agent is said to be “rationally selected or designed” when the agent is chosen based on the configuration of the particular protein. For example, one skilled in the art can readily adapt currently available procedures to generate peptides, pharmaceutical agents and the like capable of binding to a specific peptide sequence in order to generate rationally designed antipeptide peptides, for example see Hurby et al., Application of Synthetic Peptides: Antisense Peptides,”  In Synthetic Peptides, A User&#39;s Guide , W. H. Freeman, NY (1992), pp. 289-307, and Kaspczak et al.,  Biochemistry  28:9230-8 (1989), or pharmaceutical agents, or the like.  
      In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one of the ORFs or EMFs of the present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control.  
      One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix formation by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulfhydryl or polymeric derivatives which have base attachment capacity.  
      Agents suitable for use in these methods usually contain 20 to 40 bases and are designed to be complementary to a region of the gene involved in transcription (triple helix—see Lee et al.,  Nucl. Acids Res.  6:3073 (1979); Cooney et al.,  Science  241:456 (1988); and Dervan et al.,  Science  251: 1360 (1991)) or to the mRNA itself (antisense—Okano,  J. Neurochem.  56:560 (1991);  Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression , CRC Press, Boca Raton, Fla. (1988)). Triple helix—formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide and other DNA binding agents.  
      Agents which bind to a protein encoded by one of the ORFs of the present invention can be used as a diagnostic agent, in the control of bacterial infection by modulating the activity of the protein encoded by the ORF. Agents which bind to a protein encoded by one of the ORFs of the present invention can be formulated using known techniques to generate a pharmaceutical composition for use in controlling  Haemophilus  growth and infection.  
      5. Vaccine and Pharmaceutical Composition  
      The present invention further provides pharmaceutical agents which can be used to modulate the growth of  Haemophilus influenzae , or another related organism, in vivo or in vitro. As used herein, a “pharmaceutical agent” is defined as a composition of matter which can be formulated using known techniques to provide a pharmaceutical compositions. As used herein, the “pharmaceutical agents of the present invention” refers the pharmaceutical agents which are derived from the proteins encoded by the ORFs of the present invention or are agents which are identified using the herein described assays.  
      As used herein, a pharmaceutical agent is said to “modulated the growth of  Haemophilus  sp., or a related organism, in vivo or in vitro,” when the agent reduces the rate of growth, rate of division, or viability of the organism in question. The pharmaceutical agents of the present invention can modulate the growth of an organism in many fashions, although an understanding of the underlying mechanism of action is not needed to practice the use of the pharmaceutical agents of the present invention. Some agents will modulate the growth by binding to an important protein thus blocking the biological activity of the protein, while other agents may bind to a component of the outer surface of the organism blocking attachment or rendering the organism more prone to act the bodies nature immune system. Alternatively, the agent may be comprise a protein encoded by one of the ORFs of the present invention and serve as a vaccine. The development and use of a vaccine based on outer membrane components, such as the LPS, are well known in the art.  
      As used herein, a “related organism” is a broad term which refers to any organism whose growth can be modulated by one of the pharmaceutical agents of the present invention. In general, such an organism will contain a homolog of the protein which is the target of the pharmaceutical agent or the protein used as a vaccine. As such, related organism do not need to be bacterial but may be fungal or viral pathogens.  
      The pharmaceutical agents and compositions of the present invention may be administered in a convenient manner such as by the oral, topical, intravenous, intraperitoneal, intramuscular, subcutaneous, intranasal or intradermal routes. The pharmaceutical compositions are administered in an amount which is effective for treating and/or prophylaxis of the specific indication. In general, they are administered in an amount of at least about 10 μg/kg body weight and in most cases they will be administered in an amount not in excess of about 8 mg/Kg body weight per day. In most cases, the dosage is from about 10 μg/kg to about 1 mg/kg body weight daily, taking into account the routes of administration, symptoms, etc.  
      The agents of the present invention can be used in native form or can be modified to form a chemical derivative. As used herein, a molecule is said to be a “chemical derivative” of another molecule when it contains additional chemical moieties not normally a part of the molecule. Such moieties may improve the molecule&#39;s solubility, absorption, biological half life, etc. The moieties may alternatively decrease the toxicity of the molecule, eliminate or attenuate any undesirable side effect of the molecule, etc. Moieties capable of mediating such effects are disclosed in  Remington&#39;s Pharmaceutical Sciences  (1980).  
      For example, a change in the immunological character of the functional derivative, such as affinity for a given antibody, is measured by a competitive type immunoassay. Changes in immunomodulation activity are measured by the appropriate assay. Modifications of such protein properties as redox or thermal stability, biological half-life, hydrophobicity, susceptibility to proteolytic degradation or the tendency to aggregate with carriers or into multimers are assayed by methods well known to the ordinarily skilled artisan.  
      The therapeutic effects of the agents of the present invention may be obtained by providing the agent to a patient by any suitable means (i.e., inhalation, intravenously, intramuscularly, subcutaneously, enterally, or parenterally). It is preferred to administer the agent of the present invention so as to achieve an effective concentration within the blood or tissue in which the growth of the organism is to be controlled.  
      To achieve an effective blood concentration, the preferred method is to administer the agent by injection. The administration may be by continuous infusion, or by single or multiple injections.  
      In providing a patient with one of the agents of the present invention, the dosage of the administered agent will vary depending upon such factors as the patient&#39;s age, weight, height, sex, general medical condition, previous medical history, etc. In general, it is desirable to provide the recipient with a dosage of agent which is in the range of from about 1 pg/kg to 10 mg/kg (body weight of patient), although, a lower or higher dosage may be administered. The therapeutically effective dose can be lowered by using combinations of the agents of the present invention or another agent.  
      As used herein, two or more compounds or agents are said to be administered “in combination” with each other when either (1) the physiological effects of each compound, or (2) the serum concentrations of each compound can be measured at the same time. The composition of the present invention can be administered concurrently with, prior to, or following the administration of the other agent.  
      The agents of the present invention are intended to be provided to recipient subjects in an amount sufficient to decrease the rate of growth (as defined above) of the target organism.  
      The administration of the agent(s) of the invention may be for either a “prophylactic” or “therapeutic” purpose. When provided prophylactically, the agent(s) are provided in advance of any symptoms indicative of the organisms growth. The prophylactic administration of the agent(s) serves to prevent, attenuate, or decrease the rate of onset of any subsequent infection. When provided therapeutically, the agent(s) are provided at (or shortly after) the onset of an indication of infection. The therapeutic administration of the compound(s) serves to attenuate the pathological symptoms of the infection and to increase the rate of recovery.  
      The agents of the present invention are administered to the mammal in a pharmaceutically acceptable form and in a therapeutically effective concentration. A composition is said to be “pharmacologically acceptable” if its administration can be tolerated by a recipient patient. Such an agent is said to be administered in a “therapeutically effective amount” if the amount administered is physiologically significant. An agent is physiologically significant if its presence results in a detectable change in the physiology of a recipient patient.  
      The agents of the present invention can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby these materials, or their functional derivatives, are combined in admixture with a pharmaceutically acceptable carrier vehicle. Suitable vehicles and their formulation, inclusive of other human proteins, e.g., human serum albumin, are described, for example, in  Remington&#39;s Pharmaceutical Sciences  (16th ed., Osol, A., Ed., Mack, Easton Pa. (1980)). In order to form a pharmaceutically acceptable composition suitable for effective administration, such compositions will contain an effective amount of one or more of the agents of the present invention, together with a suitable amount of carrier vehicle.  
      Additional pharmaceutical methods may be employed to control the duration of action. Control release preparations may be achieved through the use of polymers to complex or absorb one or more of the agents of the present invention. The controlled delivery may be exercised by selecting appropriate macromolecules (for example polyesters, polyamino acids, polyvinyl, pyrrolidone, ethylenevinylacetate, methylcellulose, carboxymethylcellulose, or protamine, sulfate) and the concentration of macromolecules as well as the methods of incorporation in order to control release. Another possible method to control the duration of action by controlled release preparations is to incorporate agents of the present invention into particles of a polymeric material such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylene vinylacetate copolymers. Alternatively, instead of incorporating these agents into polymeric particles, it is possible to entrap these materials in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatine-microcapsules and poly(methylmethacylate) microcapsules, respectively, or in colloidal drug delivery systems, for example, liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules or in macroemulsions. Such techniques are disclosed in  Remington&#39;s Pharmaceutical Sciences  (1980).  
      The invention further provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In addition, the agents of the present invention may be employed in conjunction with other therapeutic compounds.  
      6. Shot-Gun Approach to Megabase DNA Sequencing  
      The present invention further provides the first demonstration that a sequence of greater than one megabase can be sequenced using a random shotgun approach. This procedure, described in detail in the examples that follow, has eliminated the up front cost of isolating and ordering overlapping or contiguous subclones prior to the start of the sequencing protocols.  
      Certain aspects of the present invention are described in greater detail in the non-limiting Examples that follow.  
     EXAMPLES  
      Experimental Design and Methods  
      1. Shotgun Sequencing Strategy  
      The overall strategy for a shotgun approach to whole genome sequencing is outlined in Table 3. The theory of shotgun sequencing follows from the Lander and Waterman (Landerman and Waterman,  Genomics  2: 231 (1988)) application of the equation for the Poisson distribution p x =m x e −m /x!, where x is the number of occurrences of an event, m is the mean number of occurrences, and p x  is the probability that any given base is not sequenced after a certain amount of random sequence has been generated. If L is the genome length, n is the number of clone insert ends sequenced, and w is the sequencing read length, then m=nw/L, and the probability that no clone originates at any of the w bases preceding a given base, i.e., the probability that the base is not sequenced, is p 0 =e −m . Using the fold coverage as the unit for m, one sees that after 1.8 Mb of sequence has been randomly generated, m=1, representing 1× coverage. In this case, p 0 =e −1 =0.37, thus approximately 37% is unsequenced. For example, 5× coverage (approximately 9500 clones sequenced from both insert ends and an average sequence read length of 460 bp) yields p 0 =e −5 =0.0067, or 0.67% unsequenced. The total gap length is Le −m , and the average gap size is L/n. 5× coverage would leave about 128 gaps averaging about 100 bp in size. The treatment is essentially that of Lander and Waterman,  Genomics  2:231 (1988). Table 4 illustrates the coverage for a 1.9 Mb genome with an average fragment size of 460 bp.  
      2. Random Library Construction  
      In order to approximate the random model described above during actual sequencing, a nearly ideal library of cloned genomic fragment is required. The following library construction procedure was developed to achieve this.  
       H. influenzae  Rd KW20 DNA was prepared by phenol extraction. A mixture (3.3 ml) containing 600 μg DNA, 300 mM sodium acetate, 10 mM Tris-HCl, 1 mM Na-EDTA, 30% glycerol was sonicated (Branson Model 450 Sonicator) at the lowest energy setting for 1 min. at 0° using a 3 mm probe. The DNA was ethanol precipitated and redissolved in 500 μl TE buffer. To create blunt-ends, a 100 μl aliquot was digested for 10 min at 30° in 200 μl BAL31 buffer with 5 units BAL31 nuclease (New England BioLabs). The DNA was phenol-extracted, ethanol-precipitated, redissolved in 100 μl TE buffer, electrophoresed on a 1.0% low melting agarose gel, and the 1.6-2.0 kb size fraction was excised, phenol-extracted, and redissolved in 20 μl TE buffer. A two-step ligation procedure was used to produce a plasmid library with 97% insert of which &gt;99% Y were single inserts. The first ligation mixture (50 μl) contained 2 μg of DNA fragments, 2 μg SmaI/BAP pUC18 DNA (Pharmacia), and 10 units T4 ligase (GIBCO/BRL), and incubation was at 14° for 4 hr. After phenol extraction and ethanol precipitation, the DNA was dissolved in 20 μl TE buffer and electrophoresed on a 1.0% low melting agarose gel. A ladder of ethidium bromide-stained linear bands, identified by size as insert (i), vector (v), v+i, v+2i, v+3i, . . . was visualized by 360 nm UV light, and the v+i DNA was excised and recovered in 20 μI TE. The v+i DNA was blunt-ended by T4 polymerase treatment for 5 min. at 37° in a reaction mixture (50 μl) containing the v+i linears, 500 μM each of the 4 dNTP&#39;s, and 9 units of T4 polymerase (New England BioLabs) under recommended buffer conditions. After phenol extraction and ethanol precipitation the repaired v+i linears were dissolved in 20 μl TE. The final ligation to produce circles was carried out in a 50 μl reaction containing 5 μl of v+i linears and 5 units of T4 ligase at 14° overnight. After 10 min. at 70° the reaction mixture was stored at −20°.  
      This two-stage procedure resulted in a molecularly random collection of single-insert plasmid recombinants with minimal contamination from double-insert chimeras (&lt;1%) or free vector (&lt;3%). Since deviation from randomness is most likely to occur during cloning,  E. coli  host cells deficient in all recombination and restriction functions (A. Greener,  Strategies  3 (1):5 (1990)) were used to prevent rearrangements, deletions, and loss of clones by restriction. Transformed cells were plated directly on antibiotic diffusion plates to avoid the usual broth recovery phase which allows multiplication and selection of the most rapidly growing cells. Plating occured as follows:  
      A 100 μl aliquot of Epicurian Coli SURE II Supercompetent Cells (Stratagene 200152) was thawed on ice and transferred to a chilled Falcon 2059 tube on ice. A 1.7 μl aliquot of 1.42 M β-mercaptoethanol was added to the aliquot of cells to a final concentration of 25 mM. Cells were incubated on ice for 10 min. A 1 μl aliquot of the final ligation was added to the cells and incubated on ice for 30 min. The cells were heat pulsed for 30 sec. at 42° and placed back on ice for 2 min. The outgrowth period in liquid culture was eliminated from this protocol in order to minimize the preferential growth of any given transformed cell. Instead the transformation were plated directly on a nutrient rich SOB plate containing a 5 ml bottom layer of SOB agar (1.5% SOB agar: 20 g tryptone, 5 g yeast extract, 0.5 g NaCl, 1.5% Difco Agar/L). The 5 ml bottom layer is supplemented with 0.4 ml ampicillin (50 mg/ml)/100 ml SOB agar. The 15 ml top layer of SOB agar is supplemented with 1 ml X-Gal (2%), 1 ml MgCl 2  (1 M), and 1 ml MgSO 4 /100 ml SOB agar. The 15 ml top layer was poured just prior to plating. Our titer was approximately 100 colonies/10 μl aliquot of transformation.  
      All colonies were picked for template preparation regardless of size. Only clones lost due to “poison” DNA or deleterious gene products would be deleted from the library, resulting in a slight increase in gap number over that expected.  
      In order to evaluate the quality of the  H. influenzae  library, sequence data were obtained from approximately 4000 templates using the M13-21 primer. The random sequence fragments were assembled using the AutoAssembler™ software (Applied Biosystems division of Perkin-Elmer (AB)) after obtaining 1300, 1800, 2500, 3200, and 3800 sequence fragments, and the number of unique assembled base pairs was determined. Based on the equations described above, an ideal plot of the number of base pairs remaining to be sequenced as a function of the # of sequenced fragments obtained with an average read length of 460 bp for a 2.5×10 6  and a 1.9×10 6  bp genome was determined ( FIG. 3 ). The progression of assembly was plotted using the actual data obtained from the assembly of up to 3800 sequence fragments and compared the data that is provided in the ideal plot ( FIG. 3 ).  FIG. 3  illustrates that there was essentially no deviation of the actual assembly data from the ideal plot, indicating that we had constructed close to an ideal random library with minimal contamination from double insert chimeras and free of vector.  
      3. Random DNA Sequencing  
      High quality double stranded DNA plasmid templates (19,687) were prepared using a “boiling bead” method developed in collaboration with Advanced Genetic Technology Corp. (Gaithersburg, Md.) (Adams et al.,  Science  252:1651 (1991); Adams et al.,  Nature  355:632 (1992)). Plamid preparation was performed in a 96-well format for all stages of DNA preparation from bacterial growth through final DNA purification. Template concentration was determined using Hoechst Dye and a Millipore Cytofluor. DNA concentrations were not adjusted, but low-yielding templates were identified where possible and not sequenced. Templates were also prepared from two.  H. influenzae  lambda genomic libraries. An amplified library was constructed in vector Lambda GEM-12 (Promega) and an unamplified library was constructed in Lambda DASH II (Stratagene). In particular, for the unamplified lambda library,  H. influenzae  Rd KW20 DNA (&gt;100 kb) was partially digested in a reaction mixture (200 μl) containing 50 μg DNA, 1×Sau3AI buffer, 20 units Sau3AI for 6 min. at 23°. The digested DNA was phenol-extracted and electrophoresed on a 0.5% low melting agarose gel at 2V/cm for 7 hours. Fragments from 15 to 25 kb were excised and recovered in a final volume of 6 μl. One μl of fragments was used with 1 μl of DASHII vector (Stratagene) in the recommended ligation reaction. One μl of the ligation mixture was used per packaging reaction following the recommended protocol with the Gigapack II XL Packaging Extract (Stratagene, #227711). Phage were plated directly without amplification from the packaging mixture (after dilution with 500 μl of recommended SM buffer and chloroform treatment). Yield was about 2.5×10 pfu/μl. The amplified library was prepared essentially as above except the lambda GEM-12 vector was used. After packaging, about 3.5×10 4  pfu were plated on the restrictive NM539 host. The lysate was harvested in 2 ml of SM buffer and stored frozen in 7% dimethylsulfoxide. The phage titer was approximately 1×10 9  pfu/ml.  
      Liquid lysates (10 ml) were prepared from randomly selected plaques and template was prepared on an anion-exchange resin (Qiagen). Sequencing reactions were carried out on plasmid templates using the AB Catalyst LabStation with Applied Biosystems PRISM Ready Reaction Dye Primer Cycle Sequencing Kits for the M13 forward (M13-21) and the M13 reverse (M13RP1) primers (Adams et al.,  Nature  368:474 (1994)). Dye terminator sequencing reactions were carried out on the lambda templates on a Perkin-Elmer 9600 Thermocycler using the Applied Biosystems Ready Reaction Dye Terminator Cycle Sequencing kits. T7 and SP6 primers were used to sequence the ends of the inserts from the Lambda GEM-12 library and T7 and T3 primers were used to sequence the ends of the inserts from the Lambda DASH II library. Sequencing reactions (28,643) were performed by eight individuals using an average of fourteen AB 373 DNA Sequencers per day over a 3 month period. All sequencing reactions were analyzed using the Stretch modification of the AB 373, primarily using a 34 cm well-to-read distance. The overall sequencing success rate was 84% for M13-21 sequences, 83% for M13RP1 sequences and 65% for dye-terminator reactions. The average usable read length was 485 bp for M13-21 sequences, 444 bp for M13RP1 sequences, and 375 bp for dye-terminator reactions. Table 5 summarizes the high-throughput sequencing phase of the invention.  
      Richards et al. (Richards et al.,  Automated DNA sequencing and Analysis , M. D. Adams, C. Fields, J. C. Venter, Eds. (Academic Press, London, 1994), Chap. 28.) described the value of using sequence from both ends of sequencing templates to facilitate ordering of contigs in shotgun assembly projects of lambda and cosmid clones. We balanced the desirability of both-end sequencing (including the reduced cost of lower total number of templates) against shorter read-lengths for sequencing reactions performed with the M13RP1 (reverse) primer compared to the M13-21 (forward) primer. Approximately one-half of the templates were sequenced from both ends. In total, 9,297 M13RP1 sequencing reactions were done. Random reverse sequencing reactions were done based on successful forward sequencing reactoins. Some M13RP1 sequences were obtained in a semi-directed fashion: M13-21 sequences pointing outward at the ends of contigs were chosen for M13RP1 sequencing in an effort to specifically order contigs. The semi-directed strategy was effective, and clone-based ordering formed an integral part of assembly and gap closure (see below).  
      4. Protocol for Automated Cycle Sequencing  
      The sequencing consisted of using eight ABI Catalyst robots and fourteen AB 373 Automated DNA Sequencers. The Catalyst robot is a publicly available sophisticated pipetting and temperature control robot which-has been developed specifically for DNA sequencing reactions. The Catalyst combines pre-aliquoted templates and reaction mixes consisting of deoxy- and dideoxynucleotides, the Taq thermostable DNA polymerase, fluorescently-labelled sequencing primers, and reaction buffer. Reaction mixes and templates were combined in the wells of an aluminum 96-well thermocycling plate. Thirty consecutive cycles of linear amplification (e.g., one primer synthesis) steps were performed including denaturation, annealing of primer and template, and extension of DNA synthesis. A heated lid with rubber gaskets on the thermocycling plate prevented evaporation without the need for an oil overlay.  
      Two sequencing protocols were used: dye-labelled primers and dye-labelled dideoxy chain terminators. The shotgun sequencing involves use of four dye-labelled sequencing primers, one for each of the four terminator nucleotide. Each dye-primer is labelled with a different fluorescent dye, permitting the four individual reactions to be combined into one lane of the 373 DNA Sequencer for electrophoresis, detection, and base-calling. AB currently supplies pre-mixed reaction mixes in bulk packages containing all the necessary non-template reagents for sequencing. Sequencing can be done with both plasmid and PCR-generated templates with both dye-primers and dye-terminators with approximately equal fidelity, although plasmid templates generally give longer usable sequences.  
      Thirty-two reactions were loaded per 373 Sequencer each day, for a total of 960 samples. Electrophoresis was run overnight following the manufacture&#39;s protocols, and the data was collected for twelve hours. Following electrophoresis and fluorescence detection, the AB 373 performs automatic lane tracking and base-calling. The lane-tracking was confirmed visually. Each sequence electropherogram (or fluorescence lane trace) was inspected visually and assessed for quality. Trailing sequences of low quality were removed and the sequence itself was loaded via software to a Sybase database (archived daily to a 8 mm tape). Leading vector polylinker sequence was removed automatically by software program. Average edited lengths of sequences from the standard ABI 373 were around 400 bp and depended mostly on the quality of the template used for the sequencing reaction. All of the ABI 373 Sequencers were converted to Stretch Liners, which provided a longer electrophoresis path prior to fluorescence detection, thus increasing the average number of usable bases to 500-600 bp.  
      Informatics  
      1. Data Management  
      A number of information management systems (LIMA) for a large-scale sequencing lab have been developed-(Kerlavage et al.,  Proceedings of the Twenty - Sixth Annual Hawaii International Conference on System Sciences , IEEE Computer Society Press, Washington D.C., 585 (1993)). The system used to collect and assemble the sequence data was developed using the Sybase relational data management system and was designed to automate data flow whereever possible and to reduce user error. The database stores and correlates all information collected during the entire operation from template preparation to final analysis of the genome. Because the raw output of the AB 373 Sequencers was based on a Macintosh platform and the data management system chosen was based on a Unix platform, it was necessary to design and implement a variety of multi-user, client server applications which allow the raw data as well as analysis results to flow seamlessly into the database with a minimum of user effort. A description of the software programs used for large sequence assembly and managment is provided in  FIG. 4 .  
      2. Assembly  
      An assembly engine (TIGR Assembler) was developed for the rapid and accurate assembly of thousands of sequence fragments. The AB AutoAssembler™ was modified (and named TIGR Editor) to provide a graphical interface to the electropherogram for the purpose of editing data associated with the aligned sequence file output of TIGR Assembler. TIGR Editor maintains synchrony between the electropherogram files on the Macintosh platform and the sequence data in the  H. influenzae  database on the Unix platform.  
      The TIGR assembler simultaneously clusters and assembles fragments of the genome. In order to obtain the speed necessary to assemble more than 104 fragments, the algorithm builds a hash table of 10 bp oligonucleotide subsequences to generate a list of potential sequence fragment overlaps. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Beginning with a single seed sequence fragment, TIGR Assembler extends the current contig by attempting to add the best matching fragment based on oligonucleotide content. The current contig and candidate fragment are aligned using a modified version of the Smith-Waterman algorithm (Waterman, M. S.,  Methods in Enzymology  164:765 (1988)) which provides for optimal gapped alignments. The current contig is extended by the fragment only if strict criteria for the quality of the match are met. The match criteria include the minimum length of overlap, the maximum length of an unmatched end, and the minimum percentage match. These criteria are automatically lowered by the algorithm in regions of minimal coverage and raised in regions with a possible repetitive element. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Fragments representing the boundaries of repetitive elements and potentially chimeric fragments are often rejected based on partial mismatches at the ends of alignments and excluded from the current contig. TIGR Assembler is designed to take advantage of clone size information coupled with sequencing from both ends of each template. It enforces the constraint that sequence fragments from two ends of the same template point toward one another in the contig and are located within a certain ranged of base pairs (definable for each clone based on the known clone size range for a given library). Assembly of 24,304 sequence fragments of  H. influenzae  required 30 hours of CPU time using one processor on a SPARCenter 2000 with 512 Mb of RAM. This process resulted in approximately 210 contigs. Because of the high stringency of the TIGR Assembler, all contigs were searched against each other using grasta (a modified fasta (Person and Lipman,  Proc. Natl. Acad. Sci. U.S.A.  85:2444 (1988)). In this way, additional overlaps were detected which enabled compression oof the data set into 140 contigs. The location of each fragment in the contigs and extensive information about the consensus sequence itself were loaded into the  H. influenzae  relational database.  
      3. Ordering Assembled Contigs  
      After assembly the relative positions of the 140 contigs were unknown. The contigs were ordered by asm_align. Asm_align uses a number of relationships to identify and align contigs that are adjacent to each other. Using this algorithm, the 140 contigs were placed into 42 groups totaling 42 physical gaps (no template DNA for the region) and 98 sequence gaps (template available for gap closure).  
      Ordering Contigs Separated by Physical Gaps and Achieving Closure  
      Four integrated strategies Were developed to order contigs separated by physical gaps. Oligonucleotide primers were designed and synthesized from the end of each contig group. These primers were then available for use in one or more of the strategies outlined below:  
      1. Southern analysis was done to develop a unique “fingerprint” for a subset of 72 of the above oligonucleotides. This procedure was based upon the supposition that labeled oligonucleotides homologous to the ends of adjacent contigs should hybridize to common DNA restriction fragments, and thus share a similar or identical hybridization pattern or “fingerprint”. Oligonucleotides were labeled using 50 pmoles of each 20 mer and 250 mCi of [γ- 32 P]ATP and T4 polynucleotide kinase. The labeled oligonucleotides were purified using Sephadex G-25 superfine (Pharmacia) and 107 cpm of each was used in a Southern hybridization analysis of  H. influenzae  Rd chromosomal DNA digested with one frequent cutters (AseI) and five less frequent cutters (BglII, EcoRI, PstI, XbaI, and PvuII). The DNA from each digest was fractionated on a 0.7% agarose gel and transferred to Nytran Plus nylon membranes (Schleicher &amp; Schuell). Hybridization was carried out for 16 hours at 40°. To remove non-specific signals, each blot was sequentially washed at room temperature with increasingly stringent conditions up to 0.1×SSC+0.5% SDS. Blots were exposed to a PhosphorImager cassette (Molecular Dynamics) for several hours and hybridization patterns were visually compared.  
      Adjacent contigs identified in this manner were targeted for specific PCR reactions.  
      2. Peptide links were made by searching each contig end using blastx (Altschul et al.,  J. Mol. Biol.  215:403 (1990)) against a peptide database. If the ends of two contigs matched the same database sequence in an appropriate manner, then the two contigs were tentatively considered to be adjacent to each other.  
      3. The two lambda libraries constructed from  H. influenaze  genomic DNA were probed with oligonucleotides designed from the ends of contig groups (Kirkness et al.,  Genomics  10:985 (1991)). The positive plaques were then used to prepare templates and the sequence was determined from each end of the lambda clone insert. These sequence fragments were searched using grasta against a database of all contigs. Two contigs that matched the sequence from the opposite ends of the same lambda clone were ordered. The lambda clone then provided the template for closure of the sequence gap between the adjacent contigs. The lambda clones were especially valuable for solving repeat structures.  
      4. To confirm the order of contigs found by the other approaches and establish the order of non-ordered contigs, standard and long range (XL) PCR reactions were performed as follows.  
      Standard PCR was performed in the following manner. Each reaction contained a 37 μl cocktail; 16.5 μl H 2 O, 3 μl 25 mM MgCl 2 , 8 μl of a dNTP mix (1.25 mM each dNTP), 4.5 μl 10×PCR core buffer II (Perkin Elmer), 25 ng  H. influenzae  Rd KW20 genomic DNA. The appropriate two primers ( 4 μl, 3.2  pmole/μl) were added to each reaction. A hot start was performed at 95° for 5 min followed by a 75° hold. During the hold Amplitaq DNA polymerase (Perkin Elmer) 0.3 μl in 4.3 μl H 2 O, 0.5 μl 10×PCR core buffer II, was added to each reaction. The PCR profile was 25 cycles of 94°/45 sec., denature; 55°/1 min., anneal; 72°/3 min, extension. All reactions were performed in a 96 well format on a Perkin Elmer GeneAmp PCR System 9600.  
      Long range PCR (XL PCR) was performed as follows: Each reaction contained a 35.2 μl cocktail; 12.0 μl H 2 O, 2.2 μl 25 mM Mg(OAc) 2 , 4 μl of a dNTP mix (200 μM final concentration), 12.0 μl 3.3×PCR buffer, 25 ng  H. influenzae  Rd KW20 genomic DNA. The appropriate two primers (5 μl, 3.2 pmoles/μl) was added to each reaction. A hot start was performed at 94° for 1 minute. rTth polymerase, 2.0 μl (4 U/reaction) in 2.8 μl 3.3×PCR buffer II was added to each reaction. The PCR profile was 18 cycles of 94°/15 sec., denature; 62°/8 min., anneal and extend followed by 12 cycles 94°/15 sec., denature; 62°/8 min. (increase 15 sec./cycle), anneal and extend; 72°/10 min., final extension. All reactions were performed in a 96 well format on a Perkin Elmer GeneAmp PCR System 9600.  
      Although a PCR reaction was performed for essentially every combination of physical gap ends, techniques such as Southern fingerprinting, database matching, and the probing of large insert clones were particularly valuable in ordering contigs adjacent to each other and reducing the number of combinatorial PCR reactions necessary to achieve complete gap closure. Employing these strategies to an even greater extent in future genome projects will increase the overall efficiency of complete genome closure. The number of physical gaps ordered and closed by each of these techniques is summarized in Table 5.  
      Sequence information from the ends of 15-20 kb clones is particularly suitable for gap closure, solving repeat structures, and providing general confirmation of the overall genome assembly. We were also concerned that some fragments of the  H. influenaze  genome would be non-clonable in a high copy plasmid in  E. coli . We reasoned that lytic lambda clones would provide the DNA for these segments. Approximately 100 random plaques were picked from the amplified lambda library, templates prepared, and sequence information obtained from each end. These sequences were searched (grasta) against the contigs and linked in the database to their appropriate contig, thus providing a scaffolding of lambda clones contributing additional support to the accuracy of the genome assembly ( FIG. 5 ). In addition to confirmation of the contig structure, the lambda clones provided closure for 23 physical gaps. Approximately 78% of the genome is covered by lambda clones.  
      Lambda clones were also useful for solving repeat structures. Repeat structures identified in the genome were small enough to be spanned by a single clone from the random insert library, except for the six ribosomal RNA operons and one repeat (2 copies) which was 5,340 bp in length. Oligonucleotide probes were designed from the unique flanks at the beginning of each repeat and hybridized to the lambda libraries. Positive plaques were identified for each flank and the sequence fragments from the ends of each clone were used to correctly orient the repeats within the genome.  
      The ability to distinguish and assemble the six ribosomal RNA (rRNA) operons of  H. influenaze  (16S subunit-23S subunit-5S subunit) was a test of our overall strategy to sequence and assemble a complex genome which might contain a significant number of repeat regions. The high degree of sequence similarity and the length of the six operons caused the assembly process to cluster all the underlying sequences into a few indistinguishable contigs. To determine the correct placement of the operons in the sequence, a pair of unique flanking sequences was required for each. No unique flanking sequences could be found at the left (16S rRNA) ends. This region contains the ribosomal promoter and appeared to be non-clonable in the high copy number pUC18 plasmid. However, unique sequences could be identified at the right (5S) ends. Oligonucleotide primers were designed from these six flanking regions and used to probe the two lambda libraries. For each of the six rRNA operons at least one positive plaque was identified which completely spanned the rRNA operon and contained unique flanking sequence at the 16S and 5S ends. These plaques provided the templates for obtaining the unique sequence for each of the six rRNA operons.  
      An additional confirmation of the global structure of the assembled circular genome was obtained by comparing a computer generated restriction map based on the assembled sequence for the enzymes ApaI, SmaI, and RsrII with the predicted physical map of Redfield and Lee ( Genetic Maps: locus maps of complex genomes , S. J. O&#39;Brien, Ed. Cold Spring Harbor Laboratory Press, New York, N.Y., 1990, 2110.). The restriction fragments from the sequence-derived map matched those from the physical map in size and relative order ( FIG. 5 ).  
      Editing  
      Simultaneous with the final gap filling process, each contig was edited visually by reassembling overlapping 10 kb sections of contigs using the AB AutoAssembler™ and the Fast Data Finder™ hardware. AutoAssembler™ provides a graphical interface to electropherogram data for editing. The electropherogram data was used to assign the most likely base at each position. Where a discrepancy could not be resolved or a clear assignment made, the automatic base calls were left unchanged. Individual sequence changes were written to the electropherogram files and a replication protocol (crash) was used to maintain the synchrony of sequence data between the  H. influenzae  database and the electropherogram files. Following editing, contigs were reassembled with TIGR Assembler prior to annotation.  
      Potential frameshifts identified in the course of annotating the genome were saved as reports in the database. These reports include the coordinates in a contig which the alignment software (praze) predicts to be the most likely location of a missing or inserted base and a representation of the sequence alignment containing the frameshift. Apparent frameshifts were used to indicate areas of the sequence which may require further editing. Frameshifts were not corrected in cases where clear electropherogram data disagreed with a frameshift. Frameshift editing was performed with TIGR Editor.  
      The rRNA and other repeat regions precluded complete assembly of the circular genome with TIGR Assembler. Final assembly of the genome was accomplished using comb_asm which splices together contigs based on short overlaps.  
      Accuracy of the Genome Sequence  
      The accuracy of the  H. influenaze  genome sequence is difficult to quantitate because there is very little previously determined  H. influenaze  sequence and most of these sequences are from other strains. There are, however, three parameters of accuracy that can be applied to the data. First, the number of apparent frameshifts in predicted  H. influenaze  genes, based on database similarities, is 148. Some of these apparent frameshifts may be in the database sequences rather than in ours, particularly considering that 49 of the apparent frameshifts are based on matches to hypothetical proteins from other organisms. Second, there are 188 bases in the genome that remain as N ambiguities (1/9,735 bp). Combining these two types of “known” errors, we can calculate a maximum sequence accuracy of 99.98%. The average coverage is 6.5× and less than 1% of the genome is single-fold coverage.  
      Identifying Genes  
      An attempt was made to predict all of the coding regions of the  H. influenzae  Rd genome and identify genes, tRNAs and rRNAs, as well as other features of the DNA sequence (e.g., repeats, regulatory sites, replication origin sites, nucleotide composition). A description of some of the readily apparent sequence features is provided below.  
      The  H. influenaze  Rd genome is a circular chromosome of 1,830,121 bp. The overall G/C nucleotide content is approximately 38% (A=31%, C=19%, G=19%, T=31%, IUB=0.035%). The G/C content of the genome was examined with several window lengths to look for global structural features. With a window of 5,000 bp, the G/C content is relatively even except for 7 large G/C-rich regions and several A/T-rich regions ( FIG. 5 ). The G/C rich regions correspond to six rRNA operons and the location of a cryptic mu-like prophage. Genes for several proteins with similarity to proteins encoded by bacteriophage mu are located at approximately position 1.56-1.59 Mbp of the genome. This area of the genome has a markedly higher G/C content than average for  H. influenaze  (˜50% G/C compared to ˜38% for the rest of the genome). No significance has yet been ascertained for the source or importance of the A/T rich regions.  
      The minimal origin of replication (oriC) in  E. coli  is a 245 bp region defined by three copies of a thirteen base pair repeat containing a GATC core sequence at one end and four copies of a nine base pair repeat containing a TTAT core sequence at the other end. The GATC sites are methylation targets and control replication while the TTAT sites provide the binding sites for DnaA, the first step in the replication process ( Genes  V, B. Lewin Ed. (Oxford University Press, New York, 1994), chap. 18-19). An approximately 281 bp sequence (602,483-602,764) whose limits are defined by these same core sequences appears to define the origin of replication in  H. influenaze  Rd. These coordinates lie between sets of ribosomal operons rrnF, rrnE, rrnD and rrnA, rrnB, rrnC. These two groups of ribosomal operons are transcribed in opposite directions and the placement of the origin is consistent with their polarity for transcription. Termination of  E. coli  replication is marked by two 23 bp termination sequences located ˜100 kb on either side of the midway point at which the two replication forks meet. Two potential termination sequences sharing a 10 bp core sequence with the  E. coli  termination sequence were identified in  H. influenaze  at coordinates 1,375,949-1,375,958 and 1,558,759-1,558,768. These two sets of coordinates are offset approximately 100 kb from the point 180° opposite of the proposed origin of  H. influenaze  replication.  
      Six rRNA operons were identified. Each rRNA operon contains three rRNA subunits and a variable spacer region in the order: 16S subunit—spacer region—23S subunit—5S subunit. The subunit lengths are 1539 bp, 2653 bp, and 116 bp, respectively. The G/C content of the three ribosomal subunits (50%) is higher than the genome as a whole. The G/C content of the spacer region (38%) is consistent with the remainder of the genome. The nucleotide sequence of the three rRNA subunits is 100% identical in all six ribosomal operons. The rRNA operons can be grouped into two classes based on the spacer region between the 16S and 23S sequences. The shorter of the two spacer regions is 478 bp in length (rrnB, rrnE, and rrnF) and contains the gene for tRNA Glu. The longer spacer is 723 bp in length (rrnA, rrnC, and rrnD) and contains the genes for tRNA Ile and tRNA Ala. The two sets of spacer regions are also 100% identical across each group of three operons. tRNA genes are also present at the 16S and 5S ends of two of the rRNA operons. The genes for tRNA Arg, tRNA His, and tRNA Pro are located at the 16S end of rrnE while the genes for tRNA Trp, and tRNA Asp are located at the 5S end of rrnA.  
      The predicted coding regions of the  H. influenaze  genome were initially defined by evaluating their coding potential with the program Genemark (Borodovsky and McIninch,  Computers Chem.  17(2):123 (−1993)) using codon frequency matrices derived from 122  H. influenaze  coding sequences in GenBank. The predicted coding region sequences (plus 300 bp of flanking sequence) were used in searches against a database of non-redundant bacterial proteins (NRBP) created specifically for the annotation. Redundancy was removed from NRBP at two stages. All DNA coding sequences were extracted from GenBank (release 85), and sequences from the same species were searched against each other. Sequences having &gt;97% similarity over regions &gt;100 nucleotides were combined. In addition, the sequences were translated and used in protein comparisons with all sequences in Swiss-Prot (release 30). Sequences belonging to the same species and having &gt;98% similarity over 33 amino acids were combined. NRBP is composed of 21,445 sequences extracted from 23,751 GenBank sequences and 11,183 Swiss-Prot sequences from 1,099 different species.  
      A total of 1,749 predicted coding regions were identified. Searches of the  H. infuenzae  predicted coding regions were performed using an algorithm that translates the query DNA sequence in the three plus-strand reading frames for searching against NRBP, identifies the protein sequences that match the query, and aligns the protein-protein matches using praze, a modified Smith-Waterman (Pearson and Lipman,  Proc. Natl. Acad. Sci. U.S.A.  85:2444 (1988)) algorithm. In cases where insertion or deletions in the DNA sequence produced a frameshift error, the alignment algorithm-started with protein regions of maximum similarity and extended the alignment to the same database match in alternative frames using the 300 bp flanking region. Regions known to contain frameswft errors were saved in the database and evaluated for possible, correction. Unidentified predicted coding regions and the remaining intergenic sequences were searched against a dataset of all available peptide sequences from Swiss-Prot, PIR, and GenBank. Identification of operon structures will be facilitated by experimental determination of transcription promoter and termination sites.  
      Each putatively identified  H. influenaze  gene was assigned to one of 102 biological role categories adapted from Riley (Riley, M.,  Microbiology Reviews  57(4):862 (1993)). Assignments were made by linking the protein sequence of the predicted coding regions with the Swiss-Prot sequences in the Riley database. Of the 1,749 predicted coding regions, 724 have no role assignment. Of these, no database match was found for 384, while 340 matched “hypothetical proteins” in the database. Role assignments were made for 1,025 of the predicted coding regions. A compilation of all the predicted coding regions, their unique identifiers, a three letter gene identifier, percent identity, percent similarity, and amino acid match length are presented in Table 1(a).  
      An annotated complete genome map of  H. influenaze  Rd is presented in FIGS.  6 (A)-(D). The map places each predicted coding region on the  H. influenaze  chromosome, indicates its direction of transcription and color codes its role assignment. Role assignments are also represented in  FIG. 5 .  
      A survey of the genes and their chromosomal organization in  H. influenaze  Rd make possible a description of the metabolic processes  H. influenaze  requires for survival as a free living organism, the nutritional requirements for its growth in the laboratory, and the characteristics which make it unique from other organisms specifically as it relates to its pathogenicity and virulence. The genome would be expected to have complete complements of certain classes of genes known to be essential for life. For example, there is a one-to-one correspondence of published  E. coli  ribosomal protein sequences to potential homologs in the  H. influenaze  database. Likewise, as shown in Table 1(a), an aminoacyl tRNA-synthetase is present in the genome for each amino acid. Finally, the location of tRNA genes was mapped onto the genome. There are 54 identified tRNA genes, including representatives of all 20 amino acids.  
      In order to survive as a free living organism,  H. influenaze  must produce energy in the form of ATP via fermentation and/or electron transport. As a facultative anaerobe,  H. influenaze  Rd is known to ferment glucose, fructose, galactose, ribose, xylose and fucose (Dorocicz et al.,  J. Bactenol.  175:7142 (1993)). The genes identified in Table 1(a) indicate that transport systems are available for the uptake of these sugars via the phosphoenolpyruvate-phosphotransferase system (PTS), and via non-PTS mechanisms. Genes that specify the common phosphate-carriers Enzyme I and Hpr (ptsI and ptsH) of the PTS system were identified as well as the glucose specific crr gene. The ptsH, ptsI, and crr genes constitute the pts operon. We have not however identified the gene encoding membrane-bound glucose specific Enzyme II. The latter enzyme is required for transport of glucose by the PTS system. A complete PTS system for fructose was identified.  
      Genes encoding the complete glycolytic pathway and for the production of fermentative end products were identified. Growth utilizing anaerobic respiratory mechanisms were found by identifying genes encoding functional electron transport systems using inorganic electron acceptors such as nitrates, nitrites, and dimethylsulfoxide. Genes encoding three enzymes of the tricarboxylic acid (TCA) cycle appear to be absent from the genome. Citrate synthase, isocitrate dehydrogenase, and acordtase were not found by searching the predicted coding regions or by using the  E. coli  enzymes as peptide queries against the entire genome in translation. This provides an explanation for the very high level of glutamate (Ig/L) which is required in defined culture media (Klein and Luginbuhl,  J. Gen. Microbiol.  113:409 (1979)). Glutamate can be directed into the TCA cycle via conversion to alpha-ketoglutarate by glutamate dehydrogenase. In the absence of a complete TCA cycle, glutamate presumably serves as the source of carbon for biosynthesis of amino acids using precursors which branch from the TCA cycle. Functional electron transport systems are available for the production of ATP using oxygen as a terminal electron acceptor.  
      Previously unanswered questions regarding pathogenicity and virulence can be addressed by examining certain classes of genes such as adhesions and the lipooligosaccharide biogenesis genes. Moxon and co-workers (Weiser et al.,  Cell  59:657 (1989)) have obtained evidence that a number of these virulence-related genes contain tandem tetramer repeats which undergo frequent addition and deletion of one or more repeat units during replication such that the reading frame of the gene is changed and its expression thereby altered. It is now possible, using the complete genome sequence, to locate all such tandem repeat tracts ( FIG. 5 ) and to begin to determine their roles in phase variation of such potential virulence genes.  
       H. influenzae  Rd possesses a highly efficient natural DNA transformation system (Kahn and Smith,  J. Membrane Biol.  138:155 (1984). A unique DNA uptake sequence site, 5′ AAGTGCGGT, present in multiple copies in the genome, has been shown to be necessary for efficient DNA uptake. It is now possible to locate all of these sites and completely describe their distribution with respect to genic and intergenic regions. Fifteen genes involved in transformation have already been described and sequenced (Redfield, R.,  J. Bacteriol.  173:5612 (1991); Chandler, M.,  Proc. Natl. Acad. Sci. U.S.A  89:1616 (1992); Barouki and Smith,  J. Bacteriol.  163(2):629 (1985); Tomb et al.,  Gene  104:1 (1991); Tomb, J,  Proc. Natl. Acad. Sci. U.S.A  89:10252 (1992)). Six of the genes, coma to comF, comprise an operon which is under positive control by a 22-bp palindromic competence regulatory element (CRE) about one helix turn upstream of the promoter. The rec-2 transformation gene is also controlled by this element. It is now possible to locate additional copies of CRE in the genome and discover potential transformation genes under CRE control. In addition, it may now be possible to discover other global regulatory elements with an ease not previously possible.  
      One well-described gene regulatory system in bacteria is the “two-component” system composed of a sensor molecule that detects some sort of environmental signal and a regulator molecule that is phosphorylated by the activated form of the sensor. The regulator protein is generally a transcription factor which, when activated by the sensor, turns on or off expression of a specific set of genes (for review, see Albright et al.,  Ann. Rev. Genet.  23:311 (1989); Parkinson and Kofoid,  Ann. Rev. Genet.  26:71 (1992)). It has been estimated that  E. coli  harbors 40 sensor-regulator pairs (Albright et al.,  Ann. Rev. Genet.  23:311 (1989); Parkinson and Kofoid,  Ann. Rev. Genet.  26:71 (1992)). The  H. influenaze  genome was searched with representative proteins from each family of sensor and regulator proteins using tblastn and tfasta. Four sensor and five regulator proteins were identified with similarity to proteins from other species (Table 6). There appears to be a corresponding sensor for each regulator protein except CpxR. Searches with the CpxA protein from  E. coli  identified three of the four sensors listed in Table 6, but no additional significant matches were found. It is possible that the level of sequence similarity is low enough to be undetectable with tfasta. No representatives of the NtrC-class of regulators were found. This class of proteins interacts directly with the sigma-54 subunit of RNA polymerase, which is not present in  H. influenaze . All of the regulator proteins fall into the OmpR subclass (Albright et al.,  Ann. Rev. Genet.  23:311 (1989); Parkinson and Kofoid,  Ann. Rev. Genet.  26:71 (1992)). The phoBR and basRS genes of  H. influenaze  are adjacent to one another and presumably form an operon. The nar and arc genes are not located adjacent to one another.  
      Some of the most interesting questions that can be answered by a complete genome sequence relate to what genes or pathways are absent. The non-pathogenic  H. influenaze  Rd strain varies significantly from the pathogenic serotype b strains. Many of the differences between these two strains appear in factors affecting infectivity. For example, the eight genes which make up the fimbrial gene cluster (vanHam et al.,  Mol. Microbiol.  13:673 (1994)) involved in adhesion of bacteria to host cells are now shown to be absent in the Rd strain. The pepN and purE genes which flank the fimbrial cluster in  H. influenaze  type b strains are adjacent to one another in the Rd strain ( FIG. 7 ), suggesting that the entire fimbrial duster was excised. On a broader level, we determined which  E. coli  proteins are not in  H. influenzae  by taking advantage of a non-redundant set of protein coding genes from  E. coli , namely the University of Wisconsin Genome Project contigs in GenBank: 1,216 predicted protein sequences from GenBank accessions D10483, L10328, U00006, U00039, U14003, and U18997 (Yura et al.,  Nucleic Acids Research  20:3305 (1992); Burland et al.,  Genomics  16:551 (1993)). The minimum threshold for matches was set so that even weak matches would be scored as positive, thereby giving a minimal estimate of the  E. coli  genes not present in  H. influenaze . tblastn was used to search each of the  E. coli  proteins against the complete genome. All blast scores &gt;100 were considered matches. Altogether 627  E. coli  proteins matched at least one region of the  H. influenaze  genome and 589 proteins did not. The 589 non-matching proteins were examined and found to contain a disproportionate number of hypothetical proteins from  E. coli . Sixty-eight percent of the identified  E. coli  proteins were matched by an  H. influenaze  sequence whereas only 38% of the hypothetical proteins were matched. Proteins are annotated as hypothetical based on a lack of matches with any other known protein (Yura et al.,  Nucleic Acids Research  20:3305 (1992); Burland et al.,  Genomics  16:551 (1993)). At least two potential explanations can be offered for the over representation of hypothetical proteins among those without matches: some of the hypothetical proteins are not, in fact, translated (at least in the annotated frame), or these are  E. coli -specific proteins that are unlikely to be found in any species except those most closely related to  E. coli , for example  Salmonella typhimurium.    
      A total of 384 predicted coding regions did not display significant similarity with a six-frame translation of GenBank release 87. These unidentified coding regions were compared to one another with fasta. Several novel gene families were identified. For example, two predicted coding regions without database matches (HI0591, HI0852) share 75% identity over almost their entire lengths (139 and 143 amino acid residues respectively). Their similarity to each other but failure to match any protein available in the current databases suggest that they could represent a novel cellular function.  
      Other types of analyses can be applied to the unidentified coding regions, including hydropathy analysis, which indicates the patterns of potential membrane-spanning domains that are often conserved between members of receptor and transporter gene families, even in the absence of significant amino acid identity. Five examples of unidentified predicted coding regions that display potential transmembrane domains with a periodic pattern that is characteristic of membrane-bound channel proteins are shown in  FIG. 8 . Such information can be used to focus on specific aspects of cellular function that are affected by targeted deletion or mutation of these genes.  
      Interest in the medically important aspects of  H. influenaze  biology has focused particularly on those genes which determine virulence characteristics of the organism. Recently, the catalase gene was characterized and sequenced as a possible virulence-related gene (Bishai et al.,  J. Bacteriol.  176:2914 (1994)). A number of the genes responsible for the capsular polysaccharide have been mapped and sequenced (Kroll et al.,  Mol. Microbiol.  5(6):1549 (1991)). Several outer membrane protein genes have been identified and sequenced (Langford et al.,  J. Gen. Microbiol.  138:155 (1992)). The lipooligosaccharide component of the outer membrane and the genes of its synthetic pathway are under intensive study (Weiser et al.,  J. Bacteriol.  173:3304 (1990)). While a vaccine is available, the study of outer membrane components is motivated to some extent by the need for improved vaccines.  
      Data Availability  
      The  H. influenaze  genome sequence has been deposited in the Genome Sequence DataBase (GSDB) with the accession number LA2023. The nucleotide sequence and peptide translation of each predicted coding region with identified start and stop codons have also been accessioned by GSDB.  
      Production of an Antibody to a  Haemophilus influenzae  Protein  
      Substantially pure protein or polypeptide is isolated from the transfected or transformed cells using any one of the methods known in the art. The protein can also be produced in a recombinant prokaryotic expression system, such as  E. coli , or can by chemically synthesized. Concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/ml. Monoclonal or polyclonal antibody to the protein can then be prepared as follows:  
      Monoclonal Antibody Production by Hybridoma Fusion  
      Monoclonal antibody to epitopes of any of the peptides identified and isolated as described can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C.,  Nature  256:495 (1975) or modifications of the methods thereof. Briefly, a mouse is repetitively inoculated with a few micrograms of the selected protein over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media). The successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued. Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by immunoassay procedures, such as ELISA, as originally described by Engvall, E.,  Meth. Enzymol.  70:419 (1980), and modified methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al. Basic Methods in Molecular Biology Elsevier, New York Section 21-2 (1989).  
      Polyclonal Antibody Production by Immunization  
      Polyclonal antiserum containing antibodies to heterogenous epitopes of a single protein can be prepared by immunizing suitable animals with the expressed protein described above, which can be unmodified or modified to enhance immunogenicity. Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. For example, small molecules tend to be less immunogenic than other and may require the use of carriers and adjuvant. Also, host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable. An effective immunization protocol for rabbits can be found in Vaitukaitis, J. et al.,  J. Clin. Endocrinol. Metab.  33:988-991 (1971).  
      Booster injections can be given at regular intervals, and antiserum harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, O. et al., Chap. 19 in:  Handbook of Experimental Immunology , Wier, D., ed, Blackwell (1973). Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12 μM). Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D., Chap. 42 in:  Manual of Clinical Immunology , second edition, Rose and Friedman, eds., Amer. Soc. For Microbiology, Washington, D.C. (1980).  
      Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample.  
      Preparation of PCR Primers and Amplification of DNA  
      Various fragments of the  Haemophilus influenzae  Rd genome, such as those disclosed in Tables 1(a) and 2 can be used, in accordance with the present invention, to prepare PCR primers for a variety of uses. The PCR primers are preferably at least 15 bases, and more preferably at least 18 bases in length. When selecting a primer sequence, it is preferred that the primer pairs have approximately the same G/C ratio, so that melting temperatures are approximately the same. The PCR primers and amplified DNA of this Example find use in the Examples that follow.  
      Gene Expression from DNA Sequences Corresponding to ORFs  
      A fragment of the  Haemophilus influenzae  Rd genome provided in Tables 1(a) or 2 is introduced into an expression vector using conventional technology. (Techniques to transfer cloned sequences into expression vectors that direct protein translation in mammalian, yeast, insect or bacterial expression systems are well known in the art.) Commercially available vectors and expression systems are available from a variety of suppliers including Stratagene (La Jolla, Calif.), Promega (Madison, Wis.), and Invitrogen (San Diego, Calif.). If desired, to enhance expression and facilitate proper protein folding, the codon context and codon pairing of the sequence may be optimized for the particular expression organism, as explained by Hatfield et al., U.S. Pat. No. 5,082,767, incorporated herein by this reference.  
      The following is provided as one exemplary method to generate polypeptide(s) from cloned ORFs of the  Haemophilus  genome fragment. Since the ORF lacks a poly A sequence because of the bacterial origin of the ORF, this sequence can be added to the construct by, for example, splicing out the poly A sequence from pSG5 (Stratagene) using BglI and SalI restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXT1 (Stratagene) for use in eukaryotic expression systems. pXT1 contains the LTRs and a portion of the gag gene from Moloney Murine Leukemia Virus. The position of the LTRs in the construct allow efficient stable transfection. The vector includes the Herpes Simplex thymidine kinase promoter and the selectable neomycin gene. The  Haemophilus  DNA is obtained by PCR from the bacterial vector using oligonucleotide primers complementary to the  Haemophilus  DNA and containing restriction endonuclease sequences for PstI incorporated into the 5′ primer and BglII at the 5′ end of the corresponding  Haemophilus  DNA 3′ primer, taking care to ensure that the  Haemophilus  DNA is positioned such that its followed with the poly A sequence. The purified fragment obtained from the resulting PCR reaction is digested with PstI, blunt ended with an exonuclease, digested with BglII, purified and ligated to pXT1, now containing a poly A sequence and digested BglII.  
      The ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc., Grand Island, N.Y.) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600 ug/ml G418 (Sigma, St. Louis, Mo.). The protein is preferably released into the supernatant. However if the protein has membrane binding domains, the protein may additionally be retained within the cell or expression may be restricted to the cell surface.  
      Since it may be necessary to purify and locate the transfected product, synthetic 15-mer peptides synthesized from the predicted  Haemophilus  DNA sequence are injected into mice to generate antibody to the polypeptide encoded by the  Haemophilus  DNA.  
      If antibody production is not possible, the  Haemophilus  DNA sequence is additionally incorporated into eukaryotic expression vectors and expressed as a chimeric with, for example, β-globin. Antibody to β-globin is used to purify the chimeric. Corresponding protease cleavage sites engineered between the β-globin gene and the  Haemophilus  DNA are then used to separate the two polypeptide fragments from one another after translation. One useful expression vector for generating β-globin chimerics is pSG5 (Stratagene). This vector encodes rabbit β-globin. Intron II of the rabbit β-globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression. These techniques as described are well known to those skilled in the art of molecular biology. Standard methods are published in methods texts such as Davis et al. and many of the methods are available from the technical assistance representatives from Stratagene, Life Technologies, Inc., or Promega. Polypeptide may additionally be produced from either construct using in vitro translation systems such as In vitro Express™ Translation Kit (Stratagene).  
      While the present invention has been described in some detail for purposes of clarity and understanding, one skilled in the art will appreciate that various changes in form and detail can be made without departing from the true scope of the invention.  
      All patents, patent applications and publications referred to above are hereby incorporated by reference.  
               TABLE 1(a)                          Amino acid biosynthesis                         Glutamate family                                         HI0190   202698   204044   glutamate dehydrogenase (gdhA) { Escherichia coli }   74.1   84.4   446       HI0867   915793   917833   glutamine synthetase (glnA) { Proteus vulgaris }   70.7   85.9   467       HI1725   1792409   1789821   uridylyl transferase (glnD) { Escherichia coli }   46.6   67.8   854       HI0813   861610   860240   argininosuccinate lyase (arginosuccinase) (asal) (argH) { Escherichia coli }   73.5   84.5   457       HI1733   1799112   1800443   argininosuccinate synthetase (argG) { Escherichia coli }   78.6   87.5   438       HI0598   618753   617752   omithine carbamoyltransferase (arcB) { Pseudomonas aeruginosa }   82.3   90.7   334       HI1242   1313013   1311763   gamma-glutamyl phosphate reductase (proA) { Escherichia coli }   61.7   79.4   406       HI0902   955518   956621   glutamate 5-kinase (gamma-glutamyl kinase) (proB) { Escherichia coli }   65.7   80.2   363                         Aspartate family                                         HI0288   319209   320419   aspartate aminotransferase (aspC) { Bacillus  sp.}   31.1   53.8   349       HI1623   1684147   1685334   aspartate aminotransferase (aspC) { Escherichia coli }   62.6   79.0   396       HI0566   582379   583368   asparagine synthetase A (asnA) { Escherichia coli }   63.3   77.0   330       HI0648   690744   689632   aspartate-semialdehyde dehydrogenase (asd) { Escherichia coli }   71.9   84.9   367       HI1311   1385700   1386509   dehydrodipicolinate reductase (dapB) { Escherichia coli }   70.3   82.5   269       HI0729   779456   778212   diaminopimelate decarboxylase (dap decarboxylase) (lysA) { Pseudomonas     57.6   78.8   413                     aeruginosa }       HI0752   810250   811071   diaminopimelate epimerase (dapF) { Escherichia coli }   77.0   85.8   274       HI0256   284972   285865   dihydrodipicolinate synthetase (dapA) { Escherichia coli }   58.2   79.8   292       HI1638   1693968   1694330   lysine-sensitive aspartokinase III (lysC) { Escherichia coli }   55.3   73.2   449       HI0102   109226   108096   succinyl-diaminopimelate desuccinylase (dapE) { Escherichia coli }   61.6   79.7   374       HI1640   1696728   1695820   tetrahydrodipicolinate N-succinyltransferase (dapD) { Actinobacillus     96.7   98.5   273                     pleuropneumoniae }       HI0089   96280   93836   aspartokinase-homoserine dehydrogenase (thrA) { Serratia marcescens }   62.2   77.4   814       HI0088   93820   92879   homoserine kinase (thrB) { Serratia marcescens }   61.8   80.6   306       HI0087   92833   91559   threonine synthase (thrC) { Serratia marcescens }   67.0   80.9   425       HI1044   1107725   1105876   B12-dependent homocysteine-N5-methyltetrahydrofolate transmethylase   54.2   70.4   1217                   (metH) { Escherichia coli }       HI0122   137932   136745   beta-cystathionase (metC) { Escherichia coli }   65.4   84.1   390       HI0086   90743   89601   cystathionine gamma-synthase (metB) { Escherichia coli }   41.9   62.2   374       HI1266   1339983   1341056   homoserine acetyltransferase (met2) { Saccharomyces cerevisiae }   38.1   57.1   387       HI1708   1773488   1771221   tetrahydropteroyltriglutamate methyltransferase (metE) { Escherichia coli }   52.4   68.0   747                         Serine family                                         HI0891   942366   943628   serine hydroxymethyltransferase (serine methylase) (glyA) { Actinobacillus     85.7   93.6   419                     actinomycetemcomitans }       HI0467   486594   487823   phosphoglycerate dehydrogenase (serA) { Escherichia coli }   71.1   83.9   408       HI1170   1238587   1237502   phosphoserine aminotransferase (serC) { Escherichia coli }   53.4   72.3   358       HI1035   1097573   1098514   phosphoserine phosphatase (o-phosphoserine phosphohydrolase) (serB)   52.3   69.5   303                   { Escherichia coli }       HI1105   1165130   1166077   cysteine synthetase (cysK) { Escherichia coli }   70.0   83.9   309       HI0608   636187   636987   serine acetyltransferase (cysE) { Escherichia coli }   73.0   88.3   256                         Aromatic amino acid family                                         HI0972   1026936   1027382   3-dehydroquinase (aroQ) { Actinobacillus pleuropneumoniae }   67.1   82.5   143       HI0209   222169   223254   3-dehydroquinate synthase (aroB) { Escherichia coli }   62.1   76.7   356       HI0197   211424   212494   chorismate synthase (aroC) { Escherichia coli }   77.3   88.4   350       HI0609   637000   637812   dehydroquinase shikimate dehydrogenase { Nicotiana tabacum }   30.0   51.5   242       HI1595   1656463   1657758   enolpyruvylshikimatephosphatesynthase (aroA) { Haemophilus influenzae }   97.7   98.4   432       HI0657   698939   698124   shikimate 5-dehydrogenase (aroE) { Escherichia coli }   49.1   70.1   270       HI0208   221607   222146   shikimic acid kinase I (aroK) { Escherichia coli }   75.0   87.5   104       HI1148   1213767   1214921   chorismate mutase/prephenate dehydratase pheA polypeptide (pheA)   54.3   74.7   375                   { Escherichia coli }       HI1553   1618339   1617254   DAHP synthetase (phenylalanine repressible) (aroG) { Escherichia coli }   72.0   83.8   345       HI1293   1370448   1371578   chorismate mutase (tyrA) { Erwinia herbicola }   58.6   76.8   366       HI1392   1481917   1483470   anthranilate synthase component I (trpE) { Escherichia coli }   52.9   73.2   494       HI1393   1483718   1485554   anthranilate synthase component II (trpD) { Escherichia coli }   56.6   74.2   452       HI1174   1240757   1241335   anthranilate synthase glutamine amidotransferase (trpG) { Acinetobacter     34.0   59.0   191                     calcoaceticus }       HI1437   1519794   1520597   typtophan synthase alpha chain (trpA) { Salmonella typhimurium }   57.8   72.8   267       HI1436   1518601   1519791   tryptophan synthase, beta chain (trpB) { Escherichia coli }   82.4   90.3   391       HI0474   494758   495354   amidotransferase (hisH) { Escherichia coli }   55.9   70.3   195       HI0470   490033   490941   ATP phosphoribosyltransferase (hisG) { Escherichia coli }   72.2   82.0   295       HI0476   496124   496897   hisF cyclase (hisF) { Escherichia coli }   82.0   91.0   256       HI0472   492389   493489   histidinol-phosphate aminotransferase (hisC) { Escherichia coli }   60.1   77.5   351       HI1169   1237411   1236314   histidinol-phosphate aminotransferase (hisH) { Bacillus subtilis }   38.7   61.0   354       HI0473   493604   494689   imidazoleglycerol-phosphate dehydratase (hisB) { Escherichia coli }   65.0   80.5   353       HI0477   496900   497562   phosphoribosyl-AMP cyclohydrolase (hisIE) { Escherichia coli }   60.7   77.0   195       HI0475   495393   496139   phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase   62.9   77.1   245                   (hisA) { Escherichia coli }                         Pyruvate family                                         HI1581   1642613   1643692   alanine racemase, biosynthetic (alr) { Escherichia coli }   56.3   74.9   358                         Branched chain family                                         HI0739   791174   791968   acetohydroxy acid synthase II (ilvG) { Escherichia coli }   63.6   78.5   386       HI1591   1652923   1651205   acetolactate synthase III large chain (ilvI) { Escherichia coli }   69.1   83.9   527       HI1590   1651202   1650714   acetolactate synthase III small chain (ilvH) { Escherichia coli }   65.6   85.0   160       HI1196   1259031   1258003   branched-chain-amino-acid transaminase { Salmonella typhimurium }   32.9   49.8   298       HI0740   791969   793960   dihydroxyacid dehydrase (ilvD) { Escherichia coli }   77.9   89.5   614       HI0684   723320   724795   ketol-acid reductoisomerase (ilvC) { Escherichia coli }   81.7   89.6   491       HI0991   1047074   1047673   3-isopropylmalate dehydratase (isopropylmalate isomerase) (leuD)   71.1   86.3   197                   { Salmonella typhimurium }       HI0989   1044390   1045463   3-isopropylmalate dehydrogenase (beta-IPM dehydrogenase) (leuB)   68.0   80.1   353                   { Salmonella typhimurium }       HI0985   1040319   1039678   leuA protein (leuA) { Haemophilus influenzae }   99.5   100.0   193                 Biosynthesis of cofactors, prosthetic groups, carriers                         Biotin                                         HI1560   1625092   1623803   7,8-diamino-pelargonic acid aminotransferase (bioA) { Escherichia coli }   58.0   74.1   420       HI1559   1623791   1622652   7-keto-8-aminopelargonic acid synthetase (bioF) { Bacillus sphaericus }   33.5   56.3   370       HI1557   1622004   1621225   biotin biosynthesis; reaction prior to pimeloyl CoA (bioC) { Escherichia coli }   28.6   46.8   151       HI0645   687346   684872   biotin sulfoxide reductase (BDS reductase) (bisC) { Escherichia coli }   54.0   71.8   734       HI1024   1085538   1086535   biotin synthetase (bioB) { Escherichia coli }   59.6   77.5   307       HI1556   1621212   1620640   dethiobiotin synthase (bioD) { Bacillus sphaericus }   42.1   59.6   175       HI1449   1532932   1532207   dethiobiotin synthetase (bioD) { Escherichia coli }   41.3   62.4   217                         Folic acid                                         HI1448   1531237   1532112   5,10 methylenetetrahydrofolate reductase (metF) { Escherichia coli }   72.8   83.4   290       HI0611   640325   639480   5,10-methylene-tetrahydrofolate dehydrogenase (folD) { Escherichia coli }   67.6   82.0   278       HI0064   67257   67760   7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (folK) { Escherichia     56.3   77.8   158                     coli }       HI0459   478432   477392   aminodeoxychorismate lyase (pabC) { Escherichia coli }   40.1   66.5   243       HI1635   1691986   1691351   dedA protein (dedA) { Escherichia coli }   30.4   55.1   158       HI0901   955417   954938   dehydrofolate reductase, type I (folA) { Escherichia coli }   53.2   68.4   158       HI1339   1412130   1412954   dihydropteroate synthase (folP) { Escherichia coli }   54.5   70.9   275       HI1469   1547395   1548370   dihydropteroate synthase (folP) { Escherichia coli }   54.5   70.9   275       HI1264   1337544   1338854   folylpolyglutamate synthase (folC) { Escherichia coli }   51.7   68.4   409       HI1451   1534018   1533365   GTP cyclohydrolase I (folE) { Escherichia coli }   63.9   79.0   219       HI1173   1240715   1239732   p-aminobenzoate synthetase (pabB) { Escherichia coli }   31.0   53.6   257                         Lipoate                                         HI0026   28610   27651   lipoate biosynthesis protein A (lipA) { Escherichia coli }   73.8   84.1   321       HI0027   29302   28667   lipoate biosynthesis protein B (lipB) { Escherichia coli }   66.7   84.2   181                         Molybdopterin                                         HI1681   1743523   1743044   moaC protein (moaC) { Escherichia coli }   79.1   89.2   157       HI1682   1744628   1743618   molybdenum cofactor biosynthesis protein A (moaA) { Escherichia coli }   61.8   78.3   327       HI1373   1461582   1461376   molybdenum-pterin binding protein (mopl) { Clostridium pasteurianum }   51.5   74.2   66       HI1680   1743078   1742797   molybdopterin (MPT) converting factor, subunit 1 (moaD) { Escherichia coli }   59.3   79.0   81       HI1452   1534156   1535367   molybdopterin biosynthesis protein (chlE) { Escherichia coli }   56.4   72.5   403       HI0118   132351   133133   molybdopterin biosynthesis protein (chlN) { Escherichia coli }   27.9   52.9   135       HI1453   1535374   1536102   molybdopterin biosynthesis protein (chlN) { Escherichia coli }   63.9   78.4   241       HI1679   1742793   1742344   molybdopterin converting factor, subunit 2 (moaE) { Escherichia coli }   58.0   76.0   150       HI0846   892779   892204   molybdopterin-guanine dinucleotide (mob) { Escherichia coli }   39.4   61.7   187                         Pantothenate                                         HI0633   670462   669530   antothenate kinase (coaA) { Escherichia coli }   64.1   78.2   314                         Pyridoxine                                         HI0865   913165   913851   pyridoxamine phosphate oxidase (pdxH) { Escherichia coli }   46.0   65.3   213                         Riboflavin                                         HI0766   827249   827893   3,4-dihydroxy-2-butanone 4-phosphate synthase (ribB) { Escherichia coli }   69.6   82.7   213       HI0213   225991   226662   GTP cyclohydrolase II (ribA) { Escherichia coli }   68.0   81.4   193       HI0946   1002768   1003883   riboflavin biosynthesis protein RIBG (ribD) { Escherichia coli }   57.6   76.5   361       HI1619   1678899   1679510   riboflavin synthase alha chain (ribC) { Escherichia coli }   65.5   82.3   203       HI1306   1382553   1383071   riboflavin synthase beta chain (ribE) { Escherichia coli }   76.3   89.7   156                         Thioredoxin, glutaredoxin, glutathione                                         HI0162   177496   176129   glutathinone reductase (gor) { Escherichia coli }   74.2   85.0   450       HI1118   1181697   1181197   thioredoxin (trxA) { Anabaena  sp.}   36.6   58.5   82       HI1162   1228652   1228002   thioredoxin (trxA) { Anabaena  sp.}   33.3   61.5   39       HI0084   88470   88150   thioredoxin m (trxM) { Anacystis nidulans }   53.3   79.4   107                         Menaquinone, ubiquinone                                         HI0285   317765   316062   2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (menD)   46.8   64.4   551                   { Escherichia coli }       HI0971   1025835   1026875   4-(2′-carboxyphenyl)-4-oxybutyric acid synthase (menC) { Escherichia coli }   57.3   74.2   312       HI1192   1256548   1255916   coenzyme PQQ synthesis protein III (pqqIII) { Acinetobacter calcoaceticus }   25.4   48.6   211       HI0970   1024963   1025817   DHNA synthase (menB) { Escherichia coli }   86.7   95.1   285       HI1442   1525823   1526707   famesyldiphosphate synthase (ispA) { Escherichia coli }   53.6   71.2   297       HI0195   206694   208049   o-succinylbenzoate-CoA synthase (menE) { Escherichia coli }   46.0   66.8   426                         Heme, porphyrin                                         HI1163   1229908   1228940   ferrochelatase (visA) { Escherichia coli }   51.6   69.4   315       HI0113   119848   122079   heme utilization protein (hxuC) { Haemophilus influenzae }   26.4   46.1   695       HI0265   293930   295624   heme-hemopexin utilization (hxuB) { Haemophilus influenzae }   98.1   98.9   565       HI0604   631034   629751   hemY protein (hemY) { Escherichia coli }   38.9   64.4   355       HI0465   484621   485769   oxygen-independent coproporphyrinogen III oxidase (hemN) { Salmonella     31.5   52.3   241                     typhimurium }       HI1204   1267418   1266477   protoporphyrinogen oxidase (hemG) { Escherichia coli }   36.1   56.8   153       HI1565   1629849   1628974   protoporphyrinogen oxidase (hemG) { Escherichia coli }   59.1   72.6   203       HI0605   631035   632562   uroporphyrinogen III methylase (hemX) { Escherichia coli }   39.9   60.3   358                 Cell envelope                         Membranes, lipoproteins, porins                                         HI1585   1647711   1647247   15 kd peptidoglycan-associated lipoprotein (lpp) { Haemophilus influenzae }   94.8   95.5   154       HI0622   653682   652864   28 kDa membrane protein (hlpA) { Haemophilus influenzae }   99.6   100.0   273       HI0304   335684   337249   apolipoprotein N-acyltransferase (cute) { Escherichia coli }   45.2   64.1   497       HI0362   384880   384035   hydrophobic membrane protein { Streptococcus gordonii }   37.2   66.5   268       HI0409   428260   427478   hydrophobic membrane protein { Streptococcus gordonii )   34.4   61.3   254       HI1573   1634553   1636106   iron-regulated outer membrane protein A (iroA) { Neisseria meningitidis }   28.9   50.9   398       HI0695   736825   737646   lipoprotein (hel) { Haemophilus influenzae }   99.6   99.6   274       HI0707   749215   750429   lipoprotein (nlpD) { Escherichia coli }   48.6   64.8   364       HI0705   748419   748994   lipoprotein B (lppB) { Haemophilus somnus }   72.3   89.5   191       HI0896   946675   947916   membrane fusion protein (mtrC) { Neisseria gonorrhoeae }   30.9   53.6   337       HI0403   421547   422923   outer membrane protein P1 (ompP1) { Haemophilus influenzae }   93.0   97.2   459       HI0140   153446   154522   outer membrane protein P2 (ompP2) { Haemophilus influenzae}     96.7   97.5   361       HI1167   1234699   1235757   outer membrane protein P5 (ompA) { Haemophilus influenzae }   94.1   95.8   353       HI0906   958098   958901   prolipoprotein diacylglyceryl transferase (lgt) { Escherichia coli }   62.8   80.1   285       HI0030   31698   30838   rare lipoprotein A (rlpA) { Escherichia coli }   34.5   57.8   288       HI0924   979182   979727   rare lipoprotein B (rlpB) { Escherichia coli }   33.5   62.1   163                         Surface polysaccharides, lipopolysaccharides &amp; antigens                                         HI1563   1628153   1627302   2-dehydro-3-deoxyphosphooctonate aldolase (kdsA) { Escherichia coli }   81.3   91.5   283       HI0654   696743   695463   3-deoxy-d-manno-octulosonic-acid transferase (kdtA) { Escherichia coli }   50.7   69.9   420       HI1108   1169176   1168139   ADP-heptose-lps heptosyltransferase ll (rfaF) { Escherichia coli }   63.6   78.9   345       HI1117   1181141   1180218   ADP-L-glycero-D-mannoheptose-6-epimerase (rfaD) { Escherichia coli }   78.2   87.7   308       HI0058   59659   58898   CTP: CMP-3-deoxy-D-manno-octulosonate-cytidylyl-transferase (kdsB)   65.0   81.7   245                   { Escherichia coli }       HI0917   970233   969211   firA protein (firA) { Pasteurella multocida }   84.9   91.1   338       HI0870   919974   920723   glycosyl transferase (lgtD) { Neisseria gonorrhoeae }   30.3   55.3   200       HI1584   1646090   1647058   glycosyl transferase (lgtD) { Neisseria gonorrhoeae }   47.3   64.0   328       HI0653   695463   694996   KDTB protein (kdtB) { Escherichia coli }   52.3   75.8   153       HI1684   1746281   1747291   kpsF protein (kpsF) { Escherichia coli }   49.3   70.6   294       HI1543   1607986   1608967   lic-1 operon protein (licA) { Haemophilus influenzae }   99.1   100.0   321       HI1544   1608970   1609885   lic-1 operon protein (licB) { Haemophilus influenzae }   99.0   99.3   303       HI1545   1609845   1610543   lic-1 operon protein (licC) { Haemophilus influenzae }   96.5   99.5   198       HI1546   1610546   1611340   lic-1 operon protein (licD) { Haemophilus influenzae }   88.7   94.0   268       HI1062   1125450   1124254   lipid A disaccharide synthetase (lpxB) { Escherichia coli }   63.2   77.3   382       HI0552   571001   570096   lipooligosaccharide biosynthesis protein { Haemophilus influenzae }   98.3   99.0   298       HI0767   827911   828756   lipooligosaccharide biosynthesis protein { Haemophilus influenzae }   36.4   59.5   267       HI0869   918779   919990   lsg locus hypothetical protein (GB: M94855_1) { Haemophilus influenzae }   60.5   82.5   400       HI1706   1770127   1768916   lsg locus hypothetical protein (GB: M94855_1) { Haemophilus influenzae }   99.3   100.0   401       HI1705   1768916   1768005   lsg locus hypothetical protein (GB: M94855_2) { Haemophilus influenzae }   98.4   98.7   304       HI1704   1768000   1767322   lsg locus hypothetical protein (GB: M94855_3) { Haemophilus influenzae }   96.0   97.4   226       HI1703   1766957   1766157   lsg locus hypothetical protein (GB: M94855_4) { Haemophilus influenzae }   96.1   98.4   257       HI1702   1766142   1765261   lsg locus hypothetical protein (GB: M94855_5) { Haemophilus influenzae }   96.9   98.3   294       HI1701   1765256   1764456   lsg locus hypothetical protein (GB: M94855_6) { Haemophilus influenzae }   98.9   99.3   267       HI1700   1763577   1764341   lsg locus hypothetical protein (GB: M94855_7) { Haemophilus influenzae }   98.4   98.4   255       HI1699   1763439   1762678   lsg locus hypothetical protein (GB: M94855_8) { Haemophilus influenzae }   98.6   99.0   209       HI0263   290317   291357   opsX locus protein (opsX) { Xanthomonas campestris }   35.2   56.7   261       HI1722   1788547   1787483   rfe (CGSC No 294) protein { Escherichia coli }   59.0   77.2   344       HI1147   1212723   1213637   UDP-3-0-acyl N-acetylglcosamine deacetylase (envA) { Escherichia coli }   77.3   88.2   304       HI1063   1126278   1125493   UDP-N-acetylglucosamine acetyltransferase (lpxA) { Escherichia coli }   66.0   79.4   262       HI0875   925083   926096   UDP-N-acetylglucosamine epimerase (rffE) { Escherichia coli }   65.5   79.5   336       HI0874   923609   925021   undecaprenyl-phosphate galactosephosphotransferase (rfbP) { Salmonella     57.9   75.1   465                     typhimurium }                         Surface structures                                         HI1738   1808251   1804281   adhesin (aidA-I) { Escherichia coli }   29.3   45.8   1196       HI0119   133314   134324   adhesin B precursor (fimA) { Streptococcus parasanguis }   24.5   48.3   309       HI0364   386685   385807   adhesin B precursor (fimA) { Streptococcus parasanguis }   34.6   61.6   302       HI0332   356770   358062   cell envelope protein (oapA) { Haemophilus influenaze }   99.8   100.0   431       HI0713   757120   757425   flagellar switch protein (fliM) { Salmonella typhimurium }   34.1   61.0   41       HI1464   1542848   1542296   invasin precursor (outer membrane adhesin) (yopA) { Yersinia enterocolitica }   38.5   62.1   291       HI0333   358125   358526   opacity associated protein (oapB) { Haemophilus influenzae }   99.2   99.2   132       HI0416   436627   436836   opacity protein (opa66) { Neisseria gonorrhoeae }   74.5   90.9   55       HI1177   1243585   1243947   opacity protein (opa66) { Neisseria gonorrhoeae }   37.7   59.0   181       HI1461   1540805   1540272   opacity protein (opaD) { Neisseria meningitidis }   34.5   55.8   230       HI0300   333052   331661   pilin biogenesis protein (pilB) { Pseudomonas aeruginosa }   44.1   64.8   485       HI0919   973373   970950   protective surface antigen D15 { Haemophilus influenzae }   98.6   99.5   797                         Murein sacculus, peptidoglycan                                         HI1674   1737564   1735481   carboxy-terminal protease, penicillin-binding protein 3 (prc) { Escherichia     52.3   69.5   660                     coli }       HI1143   1208355   1209272   D-alanine-D-alanine ligase (ddlB) { Escherichia coli }   59.9   75.8   303       HI1333   1408286   1406850   D-alanyl-D-alanine carboxypeptidase (dacB) { Escherichia coli }   43.9   68.2   454       HI0066   68323   69618   N-acetylmuramoyl-L-alanine amidase (amiB) { Escherichia coli }   59.5   77.0   221       HI0383   401990   401532   PC protein (15 kd peptidoglycan-associated outer membrane lipoprotein)   100.0   100.0   153                   (pal) { Haemophilus influenzae }       HI1731   1795566   1797908   penicillin-binding protein 1B (ponB) { Escherichia coli }   47.0   67.5   767       HI0032   34810   32858   penicillin-binding protein 2 (pbp2) { Escherichia coli }   58.8   73.8   609       HI0029   30819   29641   penicillin-binding protein 5 (dacA) { Escherichia coli }   54.8   68.4   362       HI0198   212582   213439   penicillin-insensitive murein endopeptidase (mepA) { Escherichia coli }   49.3   66.7   269       HI1138   1201927   1203006   phospho-N-acetylmuramoyl-pentapeptide-transferas E (mraY) { Escherichia     76.7   88.9   360                     coli }       HI0038   40689   41741   rod shape-determining protein (mreC) { Escherichia coli }   50.3   74.5   293       HI0031   32865   31753   rod shape-determining protein (mreB) { Escherichia coli }   63.1   80.7   358       HI0037   39473   40606   rod shape-determining protein (mreB) { Escherichia coli }   79.6   89.9   347       HI0039   41744   42229   rod shape-determining protein (mreD) { Escherichia coli }   40.6   71.6   154       HI0831   878792   880570   soluble lytic murein transglycosylase (slt) { Escherichia coli }   40.4   59.3   378       HI1141   1205663   1206715   transferase, peptidoglycan synthesis (murG) { Escherichia coli }   61.7   76.0   350       HI1137   1200560   1201930   UDP-murnac-pentapeptide synthetase (murF) { Escherichia coli }   51.4   68.2   452       HI1136   1199080   1200543   UDP-MurNac-tripeptide synthetase (murE) { Escherichia coli }   55.7   72.6   463       HI0270   301245   302267   UDP-N-acetylenolpyruvoylglucosamine reductase (murB) { Escherichia coli }   57.6   75.6   340       HI1083   1148434   1147163   UDP-N-acetylglucosamine enolpyruvyl transferase (murZ) { Escherichia coli }   72.4   84.5   419       HI1142   1206856   1208280   UDP-N-acetylmuramate-alanine ligase (murC) { Escherichia coli }   68.2   81.8   470       HI1139   1203132   1204442   UDP-N-acetylmuramoylalanine-D-glutamate ligase (murD) { Escherichia coli }   61.0   73.7   437       HI1499   1569479   1569826   N-acetylmuramoyl-L-alanine amidase {Bacteriophage T3}   42.9   62.2   97                 Central intermediary metabolism                         Phosphorus compounds                                         HI0697   739608   738640   exopolyphosphatase (ppx) { Escherichia coli }   55.2   76.7   318       HI0124   139861   139334   inorganic pyrophosphatase (ppa) { Escherichia coli }   36.3   50.3   157       HI0647   689574   688637   lysophospholipase L2 (pldB) { Escherichia coli }   31.2   53.1   317                         Sulfur metabolism                                         HI1374   1462019   1461693   desulfoviridin gamma subunit (dsvC) { Desulfovibrio vulgaris }   36.0   58.0   99       HI0807   854438   853741   putative arylsulfatase regulatory protein (aslB) { Escherichia coli }   47.4   67.0   381       HI0561   578539   577856   sulfite synthesis pathway protein (cysQ) { Escherichia coli }   35.9   56.0   205                         Polyamine biosynthesis                                         HI0099   106307   107374   nucleotide binding protein (potG) { Escherichia coli }   42.6   66.9   340       HI0593   614187   612028   ornithine decarboxylase (speF) { Escherichia coli }   66.4   80.2   717                         Polysaccharides - (cytoplasmic)                                         HI1360   1436170   1438359   1,4-alpha-glucan branching enzyme (glgB) { Escherichia coli }   64.5   80.1   723       HI1362   1440427   1441758   ADP-glucose synthetase (glgC) { Escherichia coli }   55.0   74.3   407       HI1364   1443545   1446007   alpha-glucan phosphorylase (glgP) { Escherichia coli }   61.1   79.1   809       HI1361   1438458   1440434   glycogen operon protein(glgX) { Escherichia coli }   54.3   67.8   501       HI1363   1441869   1443296   glycogen synthase (glgA) { Escherichia coli }   56.2   71.2   475                         Degradation of polysaccharides                                         HI1359   1434061   1436157   amylomaltase (malQ) { Escherichia coli }   40.9   62.0   615       HI1420   1507662   1507063   endochitinase { Oryza sativa }   38.9   50.9   106                         Amino sugars                                         HI0431   452989   451160   glutamine amidotransferase (glmS) { Escherichia coli }   72.1   84.3   609       HI0141   155859   154717   N-acetylglucosamine-6-phosphate deacetylase (nagA) { Escherichia coli }   54.5   72.1   376       HI0142   156944   156135   nagB protein (nagB) { Escherichia coli }   74.2   88.1   260                         Other                                         HI0048   49257   48403   7-alpha-hydroxysteroid dehydrogenase (hdhA) { Escherichia coli }   32.4   55.1   244       HI1207   1271536   1270334   acetate kinase (ackA) { Escherichia coli }   69.1   83.9   396       HI0951   1009728   1008367   GABA transaminase (gabT){ Escherichia coli }   34.4   55.8   420       HI0111   118858   119484   glutathione transferase (bphH) { Pseudomonas  sp.}   37.6   57.4   200       HI0693   734488   735996   glycerol kinase (glpK) { Escherichia coli }   76.9   89.2   502       HI0586   606429   605161   hippuricase (hipO) { Campylobacter jejuni }   27.8   49.6   376       HI0543   564874   564575   urease (ureA) { Helicobacter heilmannii }   62.4   76.2   101       HI0539   561668   561087   urease accessory protein (UreF) { Bacillus  sp.}   31.8   54.9   194       HI0541   564179   562464   urease alpha subunit (urea amidohydrolase) (ureC) { Bacillus  sp.}   67.3   82.1   569       HI0540   562333   561779   urease protein (ureE) { Helicobacter pylori }   31.0   56.8   155       HI0538   560981   560307   urease protein (ureG) { Helicobacter pylori }   70.7   86.9   198       HI0537   560229   559447   urease protein (ureH) { Helicobacter pylori }   31.5   53.9   213       HI0542   564180   564574   urease subunit B (ureB) { Escherichia coli }   61.8   77.5   103                 Energy metabolism                         Amino acids, amines                                         HI0536   559266   557842   aspartase (aspA) { Escherichia coli }   78.2   89.1   468       HI0597   617739   616810   carbamate kinase (arcC) { Pseudomonas aeruginosa }   78.3   87.7   309       HI0747   802651   803697   L-asparaginase II (ansB) { Escherichia coli }   70.5   81.2   329       HI0290   323270   321907   L-serine deaminase (sdaA) { Escherichia coli }   68.6   83.3   454                         Sugars                                         HI0820   869307   868288   aldose 1-epimerase precursor (mutarotase) (mro) { Acinetobacter     36.8   54.7   326                     calcoaceticus }       HI0055   55016   56197   D-mannonate hydrolase (uxuA) { Escherichia coli }   72.8   85.8   394       HI1119   1181808   1182476   deoxyribose aldolase (deoC) { Mycoplasma hominis }   49.0   68.5   200       HI0615   644708   643299   fucokinase (fucK) { Escherichia coli }   41.1   64.5   459       HI0613   642828   642181   fuculose-1-phosphate aldolase (fucA) { Escherichia coli }   64.7   81.4   215       HI1014   1075981   1076610   fuculose-1-phosphate aldolase (fucA) { Escherichia coli }   32.9   51.8   163       HI0821   870510   869320   galactokinase (galK) { Haemophilus influenzae }   98.4   99.0   384       HI0145   159883   158984   glucose kinase (glk) { Streptomyces coelicolor }   33.6   53.2   303       HI0616   646595   644784   L-fucose isomerase (fucl) { Escherichia coli }   69.5   84.5   583       HI1027   1090247   1089519   L-ribulose-phosphate 4-epimerase (araD) { Escherichia coli }   72.3   81.8   231       HI1111   1173107   1171938   mal inducer biosynthesis blocker (malY) { Escherichia coli }   28.1   51.6   375       HI0143   158111   157233   N-acetylneuraminate lyase (nanA) { Escherichia coli }   36.2   61.4   291       HI0507   521330   522247   ribokinase (rbsK) { Escherichia coli }   56.0   74.8   302       HI1115   1177307   1178623   xylose isomerase (xylA) { Escherichia coli }   71.3   87.2   439       HI1116   1178629   1180161   xylulose kinase (xylulokinase) { Escherichia coli }   33.1   50.0   479                         Glycolysis                                         HI0449   470280   469342   1-phosphofructokinase (fruK) { Escherichia coli }   55.4   74.1   304       HI0984   1039579   1038617   6-phosphofructokinase (pfkA) { Escherichia coli }   74.4   84.4   319       HI0934   990636   989329   enolase (eno) { Bacillus subtilis }   65.9   78.5   413       HI0526   547668   546592   fructose-bisphosphate aldolase (fba) { Escherichia coli }   71.3   85.8   359       HI1582   1643750   1645438   glucose-6-phosphate isomerase (pgi) { Escherichia coli }   76.9   88.7   548       HI0001   1   600   glyceraldehyde-3-phosphate dehydrogenase (gapdH) { Escherichia coli }   85.8   90.3   133       HI0527   548939   547782   phosphoglycerate kinase (pgk) { Escherichia coli }   81.1   90.7   387       HI0759   820852   821533   phosphoglyceromutase (gpmA) ( Zymomonas mobilis )   58.9   74.6   222       HI1579   1639619   1641052   pyruvate kinase type II (pykA) { Escherichia coli }   77.2   87.5   480       HI0680   719664   720452   triosephosphate isomerase (tpiA) { Escherichia coli }   74.4   80.7   253                         Pyruvate dehydrogenase                                         HI1235   1303195   1301495   dihydrolipoamide acetyltransferase (aceF) { Escherichia coli }   72.8   82.4   526       HI0194   206108   205248   dihydrolipoamide acetyltransferase (acoC) { Pseudomonas putida }   27.8   49.1   235       HI1234   1301378   1299945   lipoamide dehydrogenase (lpdA) { Escherichia coli }   81.5   91.6   474       HI1236   1305918   1303261   pyruvate dehydrogenase (aceE) { Escherichia coli }   68.6   84.0   886                         TCA cycle                                         HI1668   1731748   1728899   2-oxoglutarate dehydrogenase (sucA) { Escherichia coli }   69.0   80.7   930       HI0025   27397   26393   acetate: SH-citrate lyase ligase (AMP) { Klebsiella pneumoniae }   48.9   68.4   321       HI0022   25179   23680   citrate lyase alpha chain (acyl lyase subunit) (citF) { Klebsiella pneumoniae }   72.1   86.1   469       HI0023   26068   25457   citrate lyase beta chain (acyl lyase subunit) { Klebsiella pneumoniae }   62.3   81.9   203       HI0024   26352   26068   citrate lyase gamma chain (acyl lyase subunit) (citD) { Klebsiella     52.1   71.9   97                     pneumoniae }       HI1667   1728793   1727567   dihydrolipoamide succinyltransferase (sucB) { Escherichia coli }   73.6   84.5   403       HI1403   1493925   1495316   fumarate hydratase class II (fumarase) (fumC) { Escherichia coli }   61.8   74.2   460       HI1213   1275907   1276839   malate dehydrogenase (mdh) { Escherichia coli }   78.5   85.1   303       HI1248   1317431   1319698   malic acid enzyme { Bacillus stearothermophilus }   49.5   68.3   376       HI1200   1262687   1263565   succinyl-CoA synthetase alpha-subunit (sucD) { Escherichia coli }   83.4   91.7   289       HI1199   1261518   1262684   succinyl-CoA synthetase beta-subunit (sucC) { Escherichia coli }   64.7   80.2   388                         Pentose phosphate pathway                                         HI0555   574159   572708   6-phosphogluconate dehydrogenase, decarboxylating (gnd) { Escherichia     54.0   71.1   464                     coli }       HI0560   577777   576296   glucose-6-phosphate 1-dehydrogenase (G6PD) { Synechococcus  sp.}   46.2   65.3   483       HI1025   1088660   1086666   transketolase 1 (TK 1) (tktA) { Escherichia coli }   77.1   87.5   664                         Entner-Doudoroff                                         HI0047   48381   47746   2-keto-3-deoxy-6-phosphogluconate aldolase (eda) { Escherichia coli }   37.3   63.2   193       HI0049   50201   49260   2-keto-3-deoxy-D-gluconate kinase (kdgK) { Erwinia chrysanthemi }   44.2   64.5   300                         Aerobic                                         HI1655   1715678   1713987   D-lactate dehydrogenase (dld) { Escherichia coli }   59.5   77.7   560       HI1166   1234330   1231250   D-lactate dehydrogenase (dld) { Saccharomyces cerevisiae }   27.6   47.7   427       HI0607   635168   636172   glycerol-3-phosphate dehydrogenase (gpsA) { Escherichia coli }   66.6   81.5   335       HI0749   805382   806713   NADH dehydrogenase (ndh) { Escherichia coli }   57.8   75.4   430                         Anaerobic                                         HI1049   1112944   1110527   anaerobic dimethyl sulfoxide reductase A (dmsA) { Escherichia coli }   74.0   86.3   785       HI1048   1110513   1109899   anaerobic dimethyl sulfoxide reductase B (dmsB) { Escherichia coli }   72.1   84.8   204       HI1047   1109894   1109058   anaerobic dimethyl sulfoxide reductase C (dmsC) { Escherichia coli }   41.0   65.0   287       HI0646   688485   687382   cytochrome C-type protein (torC) { Escherichia coli }   37.4   54.7   365       HI0350   374535   375134   denitrification system component (nirT) { Pseudomonas stutzeri }   51.7   71.6   176       HI0009   9878   10783   fdhE protein (fdhE) { Escherichia coli }   50.8   71.6   307       HI0006   5067   8156   formate dehydrogenase, nitrate-inducible major subunit (fdnG) { Escherichia     64.4   79.2   1016                     coli }       HI0005   4802   3993   formate dehydrogenase-N affector (fdhD) { Escherichia coli }   57.7   71.0   249       HI0008   9035   9805   formate dehydrogenase-O gamma subunit (fdol) { Escherichia coli }   52.8   72.1   195       HI0007   8161   9096   formate dehydrogenase-O, beta subunit (fdoH) { Escherichia coli }   72.2   85.6   297       HI1071   1133439   1131826   formate-dependent nitrite reductase (cytochrome C552) (nrfA)   56.7   75.3   450                   { Escherichia coli }       HI1070   1131779   1131102   formate-dependent nitrite reductase (nrfB) { Escherichia coli }   50.0   66.9   134       HI1069   1131102   1130428   formate-dependent nitrite reductase protein Fe-S centers (nrfC)   64.2   81.2   217                   { Escherichia coli }       HI1068   1130428   1129466   formate-dependent nitrite reductase transmembrane protein (nrfD)   48.2   68.4   312                   { Escherichia coli }       HI0835   882094   882529   fumarate reductase (frdC) { Escherichia coli }   49.2   72.3   129       HI0834   882093   881752   fumarate reductase 13 kDa hydrophobic protein (frdD) { Escherichia coli }   53.0   76.5   119       HI0837   885089   883293   fumarate reductase, flavoprotein subunit (frdA) { Escherichia coli }   75.4   87.2   602       HI0836   883357   882530   fumarate reductase, iron-sulfur protein (frdB) { Escherichia coli }   75.5   85.3   244       HI0681   720855   720541   glpE protein (glpE) { Escherichia coli }   43.3   63.5   103       HI0620   651184   651759   glpG protein (glpG) { Escherichia coli }   39.1   64.8   178       HI0687   729180   727492   glycerol-3-phosphate dehydrogenase, subunit A (glpA) { Escherichia coli }   69.9   82.7   531       HI0686   727529   726204   glycerol-3-phosphate dehydrogenase, subunit B (glpB) { Escherichia coli }   42.3   60.3   414       HI0685   726189   724912   glycerol-3-phosphate dehydrogenase, subunit C (glpC) { Escherichia coli }   58.8   76.0   393       HI1395   1487087   1487358   hydrogenase isoenzymes formation protein (hypC) { Escherichia coli }   63.2   81.6   76                         Electron transport                                         HI0887   936816   938552   C-type cytochrome biogenesis protein (copper tolerance) (cycZ)   48.8   67.7   557                   { Escherichia coli }       HI1078   1141318   1139756   cytochrome oxidase d subunit I (cydA) { Escherichia coli }   64.3   82.4   515       HI1077   1139738   1138605   cytochrome oxidase d subunit II (cydB) { Escherichia coli }   60.9   78.4   379       HI0529   549872   550341   ferredoxin (fdx) {Chromatium vinosum}   59.5   77.2   78       HI0374   394564   394226   ferredoxin (fdx) { Escherichia coli }   64.5   83.6   110       HI0192   205148   204627   flavodoxin (fldA) { Escherichia coli }   76.9   87.3   173       HI1365   1446272   1447807   NAD(P) transhydrogenase subunit alpha (pntA) { Escherichia coli }   73.7   84.1   509       HI1366   1447821   1449242   NAD(P) transhydrogenase subunit beta (pntB) { Escherichia coli }   80.5   87.7   462       HI1281   1355273   1354614   NAD(P)H-flavin oxidoreductase { Vibrio fischeri }   33.3   54.8   211                         Fermentation                                         HI0501   514365   515657   aldehyde dehydrogenase (aldH) { Escherichia coli }   41.2   61.8   236       HI0776   836764   836114   butyrate-acetoacetate coa-transferase subunit A (ctfA) { Clostridium     53.3   75.2   214                     acetobutylicum }       HI0186   200017   198884   glutathione-dependent formaldehyde dehydrogenase (gd-faldH) { Paracoccus     58.5   77.6   375                     denitrificans }       HI1308   1383529   1384563   hydrogenase gene region (hypE) { Alcaligenes eutrophus }   28.1   48.2   237       HI1642   1698196   1700833   phosphoenolpyruvate carboxylase (ppc) { Escherichia coli }   64.8   80.0   883       HI0181   193936   191621   pyruvate formate-lyase (pfl) { Escherichia coli }   86.1   92.9   760       HI0180   191487   190750   pyruvate formate-lyase activating enzyme (act) { Escherichia coli }   74.0   85.4   246       HI1435   1517826   1518581   short chain alcohol dehydrogenase (ORFB) { Dichelobacter nodosus }   51.9   69.2   104                         Gluconeogenesis                                         HI1651   1709919   1710917   fructose-1,6-bisphosphatase (fbp) { Escherichia coli }   70.5   84.0   331       HI0811   859038   857425   phosphoenolpyruvate carboxykinase (pckA) { Escherichia coli }   71.7   83.0   444                         ATP-proton motive force interconversion                                         HI0486   504824   504573   ATP synthase C chain (atpE) { Vibrio alginolyticus }   62.7   81.9   83       HI0487   505668   504883   ATP synthase F0 subunit a (atpB) { Escherichia coli }   58.2   78.1   261       HI0485   504520   504053   ATP synthase F0 subunit b (atpF) { Escherichia coli }   63.5   79.5   156       HI0483   503491   501953   ATP synthase F1 alpha subunit (alpA) { Escherichia coli }   86.5   94.7   513       HI0481   501081   499678   ATP synthase F1 beta subunit (atpD) { Escherichia coli }   89.3   96.1   460       HI0484   504037   503507   ATP synthase F1 delta subunit (atpH) { Escherichia coli }   58.0   78.4   176       HI0480   499645   499220   ATP synthase F1 epsilon subunit (atpC) { Escherichia coli }   59.6   75.7   136       HI0482   501934   501068   ATP synthase F1 gamma subunit (atpG) { Escherichia coli }   65.3   83.0   287       HI1277   1349508   1350221   ATP synthase subunit 3 region protein (atp) { Rhodopseudomonas blastica }   31.9   50.0   237                 Fatty acid/phospholipid metabolism                                         HI0773   834230   832896   acetyl coenzyme A acetyltransferase (thiolase) (fadA) { Clostridium     63.0   80.4   391                     acetobutylicum }       HI0428   448891   448169   fadR protein involved in fatty acid metabolism (fadR) { Escherichia coli }   47.4   68.4   234       HI1064   1126738   1126295   (3R)-hydroxymyristol acyl carrier protein dehydrase (fabZ) { Escherichia coli }   68.1   85.1   141       HI0156   171552   170827   3-ketoacyl-acyl carrier protein reductase (fabG) { Escherichia coli }   73.4   88.4   241       HI0408   427385   426441   acetyl-CoA carboxylase (accA) { Escherichia coli }   75.3   88.3   318       HI0155   170568   170341   acyl carrier protein (acpP) { Escherichia coli }   82.7   90.7   75       HI0076   82175   83032   acyl-CoA thioesterase II (tesB) { Escherichia coli }   52.3   73.1   283       HI1539   1605754   1604537   beta-ketoacyl-ACP synthase I (fabB) { Escherichia coli }   72.8   83.7   403       HI0158   174085   173138   beta-ketoacyl-acyl carrier protein synthase III (fabH) { Escherichia coli }   65.9   79.8   317       HI0973   1027538   1028002   biotin carboxyl carrier protein (accB) { Escherichia coli }   71.2   82.7   156       HI0974   1028180   1029523   biotin carboxylase (accC) { Escherichia coli }   81.5   91.3   448       HI1328   1404041   1404571   D-3-hydroxydecanoyl-(acyl carrier-protein) dehydratase (fabA) { Escherichia     79.2   91.7   168                     coli }       HI0337   362881   363234   diacylglycerol kinase (dgkA) { Escherichia coli }   50.9   71.8   110       HI0002   601   2421   long chain fatty acid coA ligase { Homo sapiens }   29.5   52.8   575       HI0157   172507   171572   malonyl coenzyme A-acyl carrier protein transacylase (fabD) { Escherichia     71.0   81.6   309                     coli }       HI1740   1811556   1810672   short chain alcohol dehydrogenase homolog (envM) { Escherichia coli }   75.3   84.9   259       HI1438   1521691   1520741   USG-1 protein (usg) { Escherichia coli }   32.7   53.9   334       HI0736   788371   787652   1-acyl-glycerol-3-phosphate acyltransferase (plsC) { Escherichia coli }   62.2   78.2   238       HI0921   975561   974698   CDP-diglyceride synthetase (cdsA) { Escherichia coli }   48.4   66.5   246       HI0750   809228   806799   glycerol-3-phosphate acyltransferase (plsB) { Escherichia coli }   57.3   75.7   804       HI0212   225946   225224   phosphatidylglycerophosphate phosphatase B (pgpB) { Escherichia coli }   35.7   60.3   220       HI0123   138207   138761   phosphatidylglycerophosphate synthase (pgsA) { Escherichia coli }   66.5   83.0   182       HI0161   175145   176014   phosphatidylserine decarboxylase proenzyme (psd) { Escherichia coli }   57.6   75.5   280       HI0427   446754   448118   phosphatidylserine synthase (pssA) { Escherichia coli }   49.2   70.8   452       HI0691   732349   733440   protein D (hpd) { Haemophilus influenzae }   98.4   99.2   364                 Purines, pyrimidines, nucleosides and nucleotides                         Purine ribonucleotide biosynthesis                                         HI1622   1682920   1684005   5′-phosphoribosyl-5-amino-4-imidazole carboxylase II (purK) { Escherichia     56.8   71.9   351                     coli }       HI1434   1517646   1516615   5′-phosphoribosyl-5-aminoimidazole synthetase (purM) { Escherichia coli }   76.5   86.7   344       HI1749   1829283   1828660   5′guanylate kinase (gmk) { Escherichia coli }   64.7   81.6   206       HI0351   375941   375300   adenylate kinase (ATP-AMP transphosphorylase) (adk) { Haemophilus     99.5   99.5   214                     influenzae }       HI0641   679574   681094   adenylosuccinate lyase (purB) { Escherichia coli }   76.5   87.9   456       HI1639   1694462   1695757   adenylosuccinate synthetase (purA) { Escherichia coli }   75.7   87.3   432       HI1210   1272783   1274297   amidophosphoribosyltransferase (purF) { Escherichia coli }   69.1   84.0   504       HI0754   812369   816328   formylglycineamide ribonucleotide synthetase (purL) { Escherichia coli }   69.7   82.0   1290       HI1594   1655627   1656460   formyltetrahydrofolate hydrolase (purU) { Escherichia coli }   72.6   85.2   277       HI0223   250532   252100   guaA protein (guaA) { Escherichia coli }   78.1   87.6   525       HI0222   248355   249818   inosine-5′-monophosphate dehydrogenase (guaB) { Acinetobacter     62.7   80.9   487                     calcoaceticus }       HI0878   928811   929233   nucleoside diphosphate kinase (ndk) { Escherichia coli }   63.0   73.9   138       HI0890   940953   942239   phosphoribosylamine-glycine ligase (purD) { Escherichia coli }   75.2   84.5   427       HI1621   1682355   1682847   phosphoribosylaminoimidazole carboxylase catalytic subunit (purE)   94.4   96.9   161                   { Haemophilus influenzae }       HI0889   939259   940854   phosphoribosylaminoimidazolecarboxamide formyltransferase (purH)   77.2   86.5   525                   { Escherichia coli }       HI1433   1516557   1515922   phosphoribosylglycinamide formyltransferase (purN) { Escherichia coli }   51.9   71.4   210       HI1615   1674317   1675261   phosphoribosylpyrophosphate synthetase (prsA) { Salmonella typhimurium }   84.1   91.1   314       HI1732   1798036   1798953   SAICAR synthetase (purC) { Streptococcus pneumoniae }   29.8   54.8   204                         Pyrimidine ribonucleotide biosyn                                         HI1406   1497997   1496981   dihydroorotate dehydrogenase (dihydroorotate oxidase) (pyrD) { Escherichia     60.7   77.4   334                     coli }       HI0274   305799   305161   orotate phosphoribosyltransferase (pyrE) { Escherichia coli }   69.0   83.6   213       HI1228   1293965   1294282   pyrF operon encoding orotidine 5′-monophosphate (OMP) decarboxylase   77.1   87.6   105                   { Escherichia coli }       HI1227   1293266   1293955   pyrF protein (pyrF) { Escherichia coli }   62.3   79.4   228       HI0461   480053   479517   uracil phosphoribosyltransferase (pyrR) { Bacillus caldolyticus }   52.2   73.9   179                         2′-deoxyribonucleotide metabolism                                         HI0075   79934   82054   anaerobic ribonucleoside-triphosphate reductase (nrdD) { Escherichia coli }   77.4   88.2   702       HI0133   146656   147240   deoxycytidine triphosphate deaminase (dcd) { Escherichia coli }   75.6   86.5   193       HI0956   1012787   1013239   deoxyuridinetriphosphatase (dut) { Escherichia coli }   75.5   90.7   151       HI1538   1604204   1604464   glutaredoxin (grx) { Escherichia coli }   69.9   79.5   83       HI1666   1726318   1727445   nrdB protein (nrdB) { Escherichia coli }   85.4   92.6   376       HI1665   1723831   1726173   ribonucleoside-diphosphate reductase 1 alpha chain (nrdA) { Escherichia coli }   83.4   92.2   761       HI1161   1227925   1226972   thioredoxin reductase (trxB) { Escherichia coli }   75.9   85.8   316       HI0907   958914   959762   thymidylate synthetase (thyA) { Escherichia coli }   35.3   55.0   264                         Salvage of nucleosides and nucleotides                                         HI0585   605064   603094   2′,3′-cyclic-nucleotide 2′-phosphodiesterase (cpdB) { Escherichia coli }   62.4   77.7   641       HI1233   1299794   1299255   adenine phosphoribosyltransferase (apt) { Escherichia coli }   66.1   83.1   177       HI0553   571120   571943   adenosine-tetraphosphatase (apaH) { Escherichia coli }   52.4   73.1   271       HI1353   1426390   1427265   cytidine deaminase (cytidine aminohydrolase) (cda) { Escherichia coli }   50.0   63.4   253       HI1222   1288579   1289628   cytidylate kinase (cmk) { Escherichia coli }   64.5   79.3   217       HI1652   1711636   1710842   cytidylate kinase (cmk) { Escherichia coli }   63.5   76.8   202       HI0520   540879   540166   purine-nucleoside phosphorylase (deoD) { Escherichia coli }   84.3   90.2   235       HI0531   552177   551599   thymidine kinase (tdk) { Escherichia coli }   68.6   82.4   188       HI1231   1297050   1296427   uracil phosphoribosyltransferase (upp) { Escherichia coli }   83.2   93.8   208       HI0282   312879   313655   uridine phosphorylase (udp) { Escherichia coli }   72.0   84.8   250       HI0676   716559   716095   xanthine guanine phosphoribosyl transferase gpt (xgprt) { Escherichia coli }   72.1   87.7   152       HI0694   736541   736077   xanthine-guanine phosphoribosyltransferase (xgprt) { Salmonella     74.0   87.7   152                     typhimurium }       HI1280   1353404   1354561   putative ATPase (mrp) { Escherichia coli }   66.0   79.0   353                         Sugar-nucleotide biosynthesis, conversions                                         HI0207   219511   221319   5′-nucleotidase (ushA) { Homo sapiens }   34.5   54.8   487       HI1282   1355378   1356061   CMP-NeuNAc synthetase (siaB) { Neisseria meningitidis }   47.1   64.3   221       HI0822   871597   870551   galactose-1-phosphate uridylyltransferase (galT) { Haemophilus influenzae }   99.1   100.0   349       HI0814   862632   861748   glucosephosphate uridylyltransferase (galU) { Escherichia coli }   74.0   86.1   287       HI0353   378461   377448   udp-glucose 4-epimerase (galactowaldenase) (galE) { Haemophilus     99.1   99.1   338                     influenzae }       HI0644   682446   683813   UDP-N-acetylglucosamine pyrophosphorylase (glmU) { Escherichia coli }   68.6   83.1   456                         Nucleotide and nucleoside interconversions                                         HI1302   1376759   1378139   deoxyguanosine triphosphate triphosphohydrolase (dgt) { Escherichia coli }   38.2   57.6   469       HI1079   1141970   1143603   pyrG protein (pyrG) { Escherichia coli }   80.4   90.5   545       HI0132   146006   146644   uridine kinase (uridine monophosphokinase) (udk) { Escherichia coli }   67.8   84.7   202                 Regulatory functions                                         HI0606   632563   635091   adenylate cyclase (cyaA) { Haemophilus influenzae }   100.0   100.0   843       HI0886   936624   935917   aerobic respiration control protein ARCA (DYE resistance protein) (arcA)   77.2   87.8   237                   { Escherichia coli }       HI0221   238723   248354   aerobic respiration control sensor protein (arcB) { Escherichia coli }   45.7   70.4   768       HI1054   1117872   1116979   araC-like transcription regulator { Streptomyces lividans }   25.7   47.7   303       HI1212   1275700   1275248   arginine repressor protein (argR) { Escherichia coli }   69.1   81.2   149       HI0237   265657   265310   arsC protein (arsC) {Plasmid R773}   38.3   56.5   114       HI0464   482094   484502   ATP-dependent proteinase (Ion) { Escherichia coli }   74.5   87.9   769       HI0336   360636   362863   ATP: GTP 3′-pyrophosphotransferase (relA) { Escherichia coli }   62.9   80.5   741       HI1130   1193658   1195126   carbon starvation protein (cstA) { Escherichia coli }   32.1   53.5   499       HI0815   862845   862657   carbon storage regulator (csrA) { Escherichia coli }   68.4   91.2   57       HI0806   853619   853063   cyclic AMP receptor protein (crp) { Haemophilus influenzae }   27.2   46.7   174       HI0959   1014161   1014832   cyclic AMP receptor protein (crp) { Haemophilus influenzae }   100.0   100.0   224       HI1203   1265444   1266412   cys regulon transcriptional activator (cysB) { Escherichia coli }   63.3   79.3   324       HI0191   204595   204158   ferric uptake regulation protein (fur) { Escherichia coli }   61.4   75.0   139       HI1457   1537858   1537391   fimbrial transcription regulation repressor (pilB) { Neisseria gonorrhoeae }   32.3   53.2   124       HI1459   1539614   1538556   fimbrial transcription regulation repressor (pilB) { Neisseria gonorrhoeae }   59.0   72.6   325       HI1263   1336661   1337548   folylpolyglutamate-dihydrofolate synthetase expression regulator (accD)   69.5   82.5   290                   { Escherichia coli }       HI1430   1512975   1513745   fumarate (and nitrate) reduction regulatory protein (fnr) { Escherichia coli }   78.8   88.8   240       HI0823   871805   872800   galactose operon repressor (galS) { Haemophilus influenzae }   99.1   99.4   332       HI0756   817661   818569   glucokinase regulator { Rattus norvegicus }   31.8   56.1   512       HI0621   651792   652556   glycerol-3-phosphate regulon repressor (glpR) { Escherichia coli }   61.5   77.4   252       HI1011   1073676   1073047   glycerol-3-phosphate regulon repressor (glpR) { Escherichia coli }   28.6   50.3   198       HI1197   1259493   1260395   glycine cleavage system transcriptional activator (gcvA) { Escherichia coli }   51.7   69.1   298       HI0013   13742   12837   GTP-binding protein (era) { Escherichia coli }   77.9   87.0   299       HI0879   930478   929309   GTP-binding protein (obg) { Bacillus subtilis }   47.7   70.9   332       HI0573   592001   591099   hydrogen peroxide-inducible activator (oxyR) { Escherichia coli }   71.1   85.9   298       HI0617   647526   646780   L-fucose operon activator (fucR) { Escherichia coli }   35.1   56.1   229       HI0401   420131   420952   lacZ expression regulator (icc) { Escherichia coli }   52.9   71.3   261       HI0225   253133   253636   leucine responsive regulatory protein (lrp) { Escherichia coli }   29.6   52.6   152       HI1602   1663150   1662653   leucine responsive regulatory protein (lrp) { Escherichia coli }   77.2   86.7   158       HI0751   809477   810103   LEXA repressor (lexA) { Escherichia coli }   68.1   85.3   202       HI1465   1542848   1542810   lipooligosaccharide protein (lex2A) { Haemophilus influenzae }   44.4   66.7   9       HI1466   1542849   1543428   lipooligosaccharide protein (lex2A) { Haemophilus influenzae }   50.0   66.7   48       HI0296   328190   327876   metF aporepressor (metJ) { Escherichia coli }   81.9   93.3   105       HI1478   1558154   1557312   molybdenum transport system alternative nitrogenase regulator (modD)   31.8   51.7   259                   { Rhodobacter capsulatus }       HI0200   214274   215227   msbB protein (msbB) { Escherichia coli }   45.3   67.0   301       HI0411   429238   430662   msbB protein (msbB) { Escherichia coli }   50.9   69.3   284       HI0712   756824   757117   negative regulator of translation (relB) { Escherichia coli }   28.3   48.3   60       HI0631   667822   668406   negative rpo regulator(mclA) { Escherichia coli }   40.1   62.9   199       HI0269   299532   301232   nitrate sensor protein (narQ) { Escherichia coli }   38.6   63.0   555       HI0728   778003   777380   nitrate/nitrite response regulator protein (narP) { Escherichia coli }   59.6   79.3   205       HI0339   363915   364250   nitrogen regulatory protein P-II (glnB) { Escherichia coli }   77.7   93.8   112       HI1747   1828067   1826037   penta-phosphate guanosine-3′-pyrophosphohydrolase (spoT) { Escherichia     58.8   76.6   675                     coli }       HI1381   1475017   1473741   phosphate regulon sensor protein (phoR) { Escherichia coli }   41.8   66.8   335       HI1382   1475709   1475017   phosphate regulon transcriptional regulatory protein (phoB) { Escherichia     52.9   71.8   227                     coli }       HI0765   827030   825768   probable nadAB transcriptional regulator (nadR) { Escherichia coli }   54.6   75.1   349       HI1641   1697003   1698115   purine nucleotide synthesis repressor protein (purR) { Escherichia coli }   55.9   74.5   328       HI0164   178405   178713   putative murein gene regulator (bolA) { Escherichia coli }   47.1   65.7   102       HI0508   522278   523273   rbs repressor (rbsR) { Escherichia coli }   48.8   71.0   329       HI0565   582225   581776   regulatory protein (asnC) { Escherichia coli }   68.0   81.0   147       HI1617   1677452   1676583   regulatory protein sfs1 involved in maltose metabolism (sfsA) { Escherichia     54.3   71.2   218                     coli }       HI0895   946128   946688   repressor for cytochrome P450 (Bm3R1) { Bacillus megaterium }   23.3   50.6   182       HI0271   302396   303238   RNA polymerase sigma-32 factor (heat shock regulatory protein F334)   70.8   86.8   281                   (rpoH) { Escherichia coli }       HI0535   555646   557532   RNA polymerase sigma-70 factor (rpoD) { Escherichia coli }   68.9   80.8   608       HI0630   667228   667794   RNA polymerase sigma-E factor (rpoE) { Escherichia coli }   73.0   87.8   189       HI1713   1781137   1779785   sensor protein for basR (basS) { Escherichia coli }   30.0   55.7   253       HI1444   1529117   1528668   stringent starvation protein (sspB) { Escherichia coli }   63.2   81.1   106       HI1445   1529755   1529120   stringent starvation protein A (sspA) { Haemophilus somnus }   76.9   87.3   212       HI1745   1815630   1814704   trans-activator of metE and-metH (metR) { Escherichia coli }   39.5   60.8   294       HI0360   382477   383121   transcription activator (tenA) { Bacillus subtilis }   27.8   48.3   208       HI0683   722643   721768   transcriptional activator protein (ilvY) { Escherichia coli }   47.4   70.3   293       HI1714   1781799   1781137   transcriptional regulatory protein (basR) { Escherichia coli }   43.5   59.7   216       HI0412   430780   431733   transcriptional regulatory protein (tyrR) { Escherichia coli }   48.2   66.8   306       HI0832   880611   880913   tryptophan repressor (trpR) { Enterobacter aerogenes }   39.8   67.0   88       HI0054   54188   54985   uxu operon regulator (uxuR) { Escherichia coli }   50.0   72.1   246       HI1109   1170415   1169255   xylose operon regluatory protein (xylR) { Escherichia coli }   57.3   75.3   384                 Replication                         DNA - replication, restr/modification, recombination                                         HI0761   822003   823136   A/G-specific adenine glycosylase (mutY) { Escherichia coli }   61.6   75.1   341       HI0995   1056674   1055313   chromosomal replication initiator protein (dnaA) { Escherichia coli }   61.7   79.7   464       HI1229   1294415   1294317   chromosomal replication initiator protein (dnaA) { Escherichia coli }   50.0   75.0   12       HI0316   345720   345151   crossover junction endodeoxyribonuclease (ruvC) { Escherichia coli }   78.5   88.3   163       HI0955   1011537   1012736   dfp protein (dfp) { Escherichia coli }   61.1   76.8   402       HI0210   223259   224116   DNA adenine methylase (dam) { Escherichia coli }   55.4   71.4   266       HI1267   1343755   1341116   DNA gyrase, subunit A (gyrA) { Escherichia coli }   70.6   84.9   859       HI0569   587397   584980   DNA gyrase, subunit B (gyrB) { Escherichia coli }   74.7   85.9   803       HI1191   1255302   1253122   DNA helicase II (uvrD) { Haemophilus influenzae }   96.8   97.5   727       HI1102   1162989   1160953   DNA ligase (lig) { Escherichia coli }   63.7   79.9   666       HI0405   423539   424207   DNA mismatch protein (mutH) { Escherichia coli }   60.4   80.7   212       HI0709   750565   753147   DNA mismatch repair protein (mutS) { Escherichia coli }   71.0   84.0   853       HI0067   69622   71508   DNA mismatch repair protein MUTL (mutL) { Escherichia coli }   50.2   67.3   612       HI0858   904919   902130   DNA polymerase I (polA) { Escherichia coli }   63.1   77.0   928       HI0994   1055297   1054200   DNA polymerase III beta-subunit (dnaN) { Escherichia coli }   62.6   80.3   366       HI0457   476761   475763   DNA polymerase III delta prime subunit (holB) { Escherichia coli }   35.3   57.4   316       HI0925   979730   980761   DNA polymerase III delta subunit (holA) { Escherichia coli }   45.2   62.0   332       HI0138   152669   151902   DNA polymerase III epsilon subunit (dnaQ) { Escherichia coli }   61.3   76.5   236       HI0741   799019   795544   DNA polymerase III, alpha chain (dnaE) { Escherichia coli }   71.9   85.7   1159       HI1402   1493690   1493259   DNA polymerase III, chi subunit (holC) { Haemophilus influenzae }   98.9   98.9   88       HI0011   11672   11271   DNA polymerase III, psi subunit (holD) { Escherichia coli }   34.4   59.2   123       HI0534   553659   555645   DNA primase (dnaG) { Escherichia coli }   56.5   73.8   571       HI1746   1826037   1823959   DNA recombinase (recG) { Escherichia coli }   66.5   80.1   693       HI0070   77166   75493   DNA repair protein (recN) { Escherichia coli }   48.6   67.3   533       HI0659   699507   700058   DNA topoisomerase I (topA) { Bacillus subtilis }   34.2   55.0   110       HI0656   698124   697570   DNA-3-methyladenine glycosidase I (tagI) { Escherichia coli }   62.6   76.0   179       HI0730   779457   781969   DNA-dependent ATPase, DNA helicase (recQ) { Escherichia coli }   62.9   77.6   589       HI0568   584860   584159   dod protein (dod) { Serratia marcescens }   81.4   93.3   210       HI0062   65230   65664   dosage-dependent dnaK suppressor protein (dksA) { Escherichia coli }   73.9   83.8   142       HI0948   1005798   1004986   formamidopyrimidine-DNA glycosylase (fpg) { Escherichia coli }   57.6   74.7   269       HI0584   602405   600519   glucose inhibited division protein (gidA) { Escherichia coli }   76.1   87.3   627       HI0488   506816   506208   glucose inhibited division protein (gidB) { Escherichia coli }   64.0   78.0   200       HI0982   1037496   1037792   Hin recombinational enhancer binding protein (fis) { Escherichia coli }   81.6   92.9   97       HI0514   528338   527565   HincII endonuclease (HincII) { Haemophilus influenzae }   98.4   98.4   258       HI1397   1491189   1490263   HindIII modification methyltransferase (hindIIIM) { Haemophilus influenzae }   99.4   99.4   309       HI1398   1492072   1491173   HindIII restriction endonuclease (hindIIIR) { Haemophilus influenzae }   99.7   99.7   300       HI0315   345085   344474   holliday junction DNA helicase (ruvA) { Escherichia coli }   58.8   79.9   203       HI0314   344463   343459   holliday junction DNA helicase (ruvB) { Escherichia coli }   80.9   90.0   330       HI0678   719064   718180   integrase/recombinase protein (xerC) { Escherichia coli }   58.0   74.4   293       HI1316   1391102   1391389   integration host factor alpha-subunit (himA) { Escherichia coli }   63.8   83.0   94       HI1224   1291400   1291681   integration host factor beta-subunit (IHF-beta) (himD) { Escherichia coli }   56.5   77.2   92       HI0404   422970   423539   methylated-DNA-protein-cysteine methyltransferase (dat1) { Bacillus     40.1   61.7   163                     subtilis }       HI0671   713369   713806   mioC protein (mioC) { Escherichia coli }   53.5   71.5   144       HI1043   1104813   1105724   modification methylase HgiDI (MHgiDI) { Herpetosiphon aurantiacus }   56.4   70.5   297       HI0515   529891   528338   modification methylase HincII (hincIIM) { Haemophilus influenzae }   98.2   98.6   502       HI0912   963611   964312   mutator mutT (AT-GC transversion) { Escherichia coli }   48.8   72.0   125       HI0193   206098   206688   negative modulator of initiation of replication (seqA) { Escherichia coli }   53.1   71.8   177       HI0548   568202   567879   primosomal protein n precursor (priB) { Escherichia coli }   57.4   75.2   101       HI0341   367532   365343   primosomal protein replication factor (priA) { Escherichia coli }   52.3   70.2   729       HI0389   406402   408321   probable ATP-dependent helicase (dinG) { Escherichia coli }   32.2   51.1   680       HI0993   1054243   1053119   recF protein (recF) { Escherichia coli }   57.0   75.8   356       HI0334   358532   359239   recO protein (recO) (Escherichia coli}   64.6   76.5   226       HI0602   621957   620896   recombinase (recA) { Haemophilus influenzae }   100.0   100.0   354       HI0061   64971   62573   recombination protein (rec2) { Haemophilus influenzae }   99.9   99.9   800       HI0445   464118   464717   recR protein (recR) { Escherichia coli }   74.9   88.4   199       HI0601   620735   620358   regulatory protein (recX) { Pseudomonas fluorescens }   28.6   50.4   117       HI0651   694862   692768   rep helicase (rep) { Escherichia coli }   66.9   82.7   669       HI1232   1299240   1297177   replication protein (dnaX) { Escherichia coli }   52.9   69.8   643       HI1580   1641089   1642600   replicative DNA helicase (dnaB) { Escherichia coli }   68.6   82.8   462       HI1042   1103812   1104813   restriction enzyme (hgiDIR) { Herpetosiphon giganteus }   44.2   63.9   350       HI1175   1241423   1242574   S-adenosylmethionine synthetase 2 (metX) { Escherichia coli }   82.3   91.7   383       HI1429   1512463   1511552   shufflon-specific DNA recombinase (rci) { Escherichia coli }   31.1   55.5   259       HI0251   281830   282333   single-stranded DNA binding protein (ssb) { Haemophilus influenzae }   95.8   98.2   168       HI1578   1639113   1638016   site-specific recombinase (rcb) { Escherichia coli }   36.3   57.0   265       HI1368   1450325   1452928   topoisomerase I (topA) { Escherichia coli }   72.0   84.3   865       HI0446   464736   466688   topoisomerase III (topB) { Escherichia coli }   65.9   79.4   645       HI1535   1599641   1601881   topoisomerase IV subunit A (parC) { Escherichia coli }   71.4   85.4   727       HI1534   1597676   1599571   topoisomerase IV subunit B (parE) { Escherichia coli }   76.5   88.6   630       HI1261   1331575   1335011   transcription-repair coupling factor (trcF) (mfd) { Escherichia coli }   64.3   82.7   1134       HI0217   232884   234038   type I restriction enzyme ecokl specificity protein (hsdS) { Escherichia coli }   36.1   58.6   394       HI0216   231281   232797   type I restriction enzyme ECOR124/3 I M protein (hsdM) { Escherichia coli }   81.2   89.3   512       HI1290   1368549   1367223   type I restriction enzyme ECOR124/3 I M protein (hsdM) { Escherichia coli }   30.4   53.7   332       HI1288   1365756   1362592   type I restriction enzyme ECOR124/3 R protein (hsdR) { Escherichia coli }   30.4   52.7   991       HI1059   1123091   1121205   type III restriction-modification ECOP15 enzyme (mod) { Escherichia coli }   36.5   55.5   384       HI0018   18087   18743   uracil DNA glycosylase (ung) { Escherichia coli }   70.2   79.5   215       HI0311   342051   342941   xprB protein (xerD) { Escherichia coli }   68.9   84.8   296                         Degradation of DNA                                         HI1695   1758680   1759312   endonuclease III (nth) { Escherichia coli }   83.4   91.9   211       HI0250   278528   281829   excinuclease ABC subunit A (uvrA) { Escherichia coli }   81.2   91.0   940       HI1250   1323924   1321888   excinuclease ABC subunit B (uvrB) { Escherichia coli }   78.0   87.7   669       HI0057   58893   57067   excinuclease ABC subunit C (uvrC) { Escherichia coli }   65.9   80.0   588       HI1380   1471626   1473044   exodeoxyribonuclease I (sbcB) { Escherichia coli }   57.5   74.9   462       HI1324   1395898   1399530   exodeoxyribonuclease V (recB) { Escherichia coli }   37.1   58.2   1165       HI0944   998895   1002257   exodeoxyribonuclease V (recC) { Escherichia coli }   40.1   61.2   1114       HI1325   1399533   1401452   exodeoxyribonuclease V (recD) { Escherichia coli }   40.0   59.3   570       HI0041   43872   43072   exonuclease III (xthA) { Escherichia coli }   71.9   83.9   267       HI0399   417972   419288   exonuclease VII, large subunit (xseA) { Escherichia coli }   57.8   74.4   437       HI1217   1280795   1282519   single-stranded-DNA-specific exonuclease (recJ) { Escherichia coli }   59.2   77.3   554                 Transcription                         RNA synthesis, modification and DNA transcription                                         HI0618   647724   650492   ATP-dependent helicase HEPA (hepA) { Escherichia coli }   53.6   73.6   968       HI0424   444751   443435   ATP-dependent RNA helicase (srmB) { Escherichia coli }   39.8   60.9   448       HI0232   260978   262816   ATP-dependent RNA helicase DEAD (deaD) { Escherichia coli }   64.0   78.6   613       HI0804   851485   852468   DNA-directed RNA polymerase alpha chain (rpoA) { Escherichia coli }   91.8   97.0   329       HI0517   534212   538870   DNA-directed RNA polymerase beta chain (rpoB) { Salmonella typhimurium }   83.3   91.9   1342       HI0516   534211   529967   DNA-directed RNA polymerase beta&#39; chain (rpoC) { Escherichia coli }   83.0   90.7   1399       HI1307   1383078   1383509   N utilization substance protein B (nusB) { Escherichia coli }   54.9   71.4   133       HI0063   65915   67269   plasmid copy number control protein (pcnB) { Escherichia coli }   55.7   73.4   404       HI0230   257702   259828   polynucleotide phosphorylase (pnp) { Escherichia coli }   74.2   86.7   708       HI0894   944630   945883   putative ATP-dependent RNA helicase (rhlB) { Escherichia coli }   73.9   84.1   410       HI1748   1828594   1828331   RNA polymerase omega subunit (rpoZ) { Escherichia coli }   64.8   76.1   88       HI1463   1542205   1541624   sigma factor (algU) { Pseudomonas aeruginosa }   27.6   48.8   168       HI0445   464118   464717   recR protein (recR) { Escherichia coli }   74.9   88.4   199       HI0601   620735   620358   regulatory protein (recX) { Pseudomonas fluorescens }   28.6   50.4   117       HI0651   694862   692768   rep helicase (rep) { Escherichia coli }   66.9   82.7   669       HI1232   1299240   1297177   replication protein (dnaX) { Escherichia coli }   52.9   69.8   643       HI1580   1641089   1642600   replicative DNA helicase (dnaB) { Escherichia coli }   68.6   82.8   462       HI1042   1103812   1104813   restriction enzyme (hgiDIR) { Herpetosiphon giganteus }   44.2   63.9   350       HI1175   1241423   1242574   S-adenosylmethionine synthetase 2 (metX) { Escherichia coli }   82.3   91.7   383       HI1429   1512463   1511552   shufflon-specific DNA recombinase (rci) { Escherichia coli }   31.1   55.5   259       HI0251   281830   282333   single-stranded DNA binding protein (ssb) { Haemophilus influenzae }   95.8   98.2   168       HI1578   1639113   1638016   site-specific recombinase (rcb) { Escherichia coli }   36.3   57.0   265       HI1368   1450325   1452928   topoisomerase I (topA) { Escherichia coli }   72.0   84.3   865       HI0446   464736   466688   topoisomerase III (topB) { Escherichia coli }   65.9   79.4   645       HI1535   1599641   1601881   topoisomerase IV subunit A (parC) { Escherichia coli }   71.4   85.4   727       HI1534   1597676   1599571   topoisomerase IV subunit B (parE) { Escherichia coli }   76.5   88.6   630       HI1261   1331575   1335011   transcription-repair coupling factor (trcF) (mfd) { Escherichia coli }   64.3   82.7   1134       HI0217   232884   234038   type I restriction enzyme ecokl specificity protein (hsdS) { Escherichia coli }   36.1   58.6   394       HI0216   231281   232797   type I restriction enzyme ECOR124/3 I M protein (hsdM) { Escherichia coli }   81.2   89.3   512       HI1290   1368549   1367223   type I restriction enzyme ECOR124/3 I M protein (hsdM) { Escherichia coli }   30.4   53.7   332       HI1288   1365756   1362592   type I restriction enzyme ECOR124/3 R protein (hsdR) { Escherichia coli }   30.4   52.7   991       HI1059   1123091   1121205   type III restriction-modilication ECOP15 enzyme (mod) { Escherichia coli }   36.5   55.5   384       HI0018   18087   18743   uracil DNA glycosylase (ung) { Escherichia coli }   70.2   79.5   215       HI0311   342051   342941   xprB protein (xerD) { Escherichia coli }   68.9   84.8   296                         Degradation of DNA                                         HI1695   1758680   1759312   endonuclease III (nth) { Escherichia coli }   83.4   91.9   211       HI0250   278528   281829   excinuclease ABC subunit A (uvrA) { Escherichia coli }   81.2   91.0   940       HI1250   1323924   1321888   excinuclease ABC subunit B (uvrB) { Escherichia coli }   78.0   87.7   669       HI0057   58893   57067   excinuclease ABC subunit C (uvrC) { Escherichia coli }   65.9   80.0   588       HI1380   1471626   1473044   exodeoxyribonuclease I (sbcB) { Escherichia coli }   57.5   74.9   462       HI1324   1395898   1399530   exodeoxyribonuclease V (recB) { Escherichia coli }   37.1   58.2   1165       HI0944   998895   1002257   exodeoxyribonuclease V (recC) { Escherichia coli }   40.1   61.2   1114       HI1325   1399533   1401452   exodeoxyribonuclease V (recD) { Escherichia coli }   40.0   59.3   570       HI0041   43872   43072   exonuclease III (xthA) { Escherichia coli }   71.9   83.9   267       HI0399   417972   419288   exonuclease VII, large subunit (xseA) { Escherichia coli }   57.8   74.4   437       HI1217   1280795   1282519   single-stranded-DNA-specific exonuclease (recJ) { Escherichia coli }   59.2   77.3   554                 Transcription                         RNA synthesis, modification and DNA transcription                                         HI0618   647724   650492   ATP-dependent helicase HEPA (hepA) { Escherichia coli }   53.6   73.6   968       HI0424   444751   443435   ATP-dependent RNA helicase (srmB) { Escherichia coli }   39.8   60.9   448       HI0232   260978   262816   ATP-dependent RNA helicase DEAD (deaD) { Escherichia coli }   64.0   78.6   613       HI0804   851485   852468   DNA-directed RNA polymerase alpha chain (rpoA) { Escherichia coli }   91.8   97.0   329       HI0517   534212   538870   DNA-directed RNA polymerase beta chain (rpoB) { Salmonella typhimurium }   83.3   91.9   1342       HI0516   534211   529967   DNA-directed RNA polymerase beta&#39; chain (rpoC) { Escherichia coli }   83.0   90.7   1399       HI1307   1383078   1383509   N utilization substance protein B (nusB) { Escherichia coli }   54.9   71.4   133       HI0063   65915   67269   plasmid copy number control protein (pcnB) { Escherichia coli }   55.7   73.4   404       HI0230   257702   2S9828   polynucleotide phosphorylase (pnp) { Escherichia coli }   74.2   86.7   708       HI0894   944630   945883   putative ATP-dependent RNA helicase (rhlB) { Escherichia coli }   73.9   84.1   410       HI1748   1828594   1828331   RNA polymerase omega subunit (rpoZ) { Escherichia coli }   64.8   76.1   88       HI1463   1542205   1541624   sigma factor (algU) { Pseudomonas aeruginosa }       HI0719   764847   765401   transcription antitermination protein (nusG) { Escherichia coli }   73.7   84.4   179       HI0571   589932   590405   transcription elongation factor (greB) { Escherichia coli }   61.5   79.5   156       HI1286   1358486   1360006   transcription factor (nusA) { Salmonella typhimurium }   70.8   84.1   499       HI0297   328437   329696   transcription termination factor rho (rho) { Escherichia coli }   87.4   95.2   419                         Degradation of RNA                                         HI0219   234848   237923   anticodon nuclease masking-agent (prrD) { Escherichia coli }   72.9   85.6   291       HI1739   1810586   1808610   exoribonuclease II (RNaseII) { Escherichia coli }   50.8   68.0   588       HI0392   411354   412550   ribonuclease D (rnd) { Escherichia coli }   41.3   65.5   365       HI0415   433540   436392   ribonuclease E (rne) { Escherichia coli }   60.3   72.3   1058       HI0139   152730   153191   ribonuclease H (rnh) { Escherichia coli }   64.9   76.0   154       HI1061   1124258   1123668   ribonuclease HII (EC 31264) (RNASE HII) { Escherichia coli }   73.7   82.8   185       HI0014   14422   13742   ribonuclease III (rnc) { Escherichia coli }   65.3   80.2   221       HI0275   306539   305826   ribonuclease PH (rph) { Escherichia coli }   78.9   87.8   237       HI1001   1063336   1063743   RNase P (mpA) { Escherichia coli }   69.7   80.7   119       HI0326   351726   352412   RNase T (mt) { Escherichia coli }   65.7   80.9   204                 Translation                         Ribosomal proteins - synthesis, modification                                         HI0518   539557   538871   ribosomal protein L1 (rpL1) { Escherichia coli }   85.6   93.4   229       HI0642   681369   681857   ribosomal protein L10 (rpL10) { Salmonella typhimurium }   80.5   89.0   165       HI0519   539990   539565   ribosomal protein L11 (rpL11) { Escherichia coli }   86.6   94.4   142       HI0980   1035484   1036371   ribosomal protein L11 methyltransferase (prmA) { Escherichia coli }   69.2   83.2   291       HI1447   1530773   1530348   ribosomal protein L13 (rpL13) { Haemophilus somnus }   94.4   95.8   142       HI0790   844379   844747   ribosomal protein L14 (rpL14) { Escherichia coli }   94.3   98.4   123       HI0799   847996   848427   ribosomal protein L15 (rpL15) { Escherichia coli }   82.6   91.0   144       HI0786   842244   842651   ribosomal protein L16 (rpL16) { Escherichia coli }   89.7   95.6   136       HI0805   852512   852895   ribosomal protein L17 (rplQ) { Escherichia coli }   89.8   92.1   127       HI0796   846938   847288   ribosomal protein L18 (rpL18) { Escherichia coli }   84.6   91.5   117       HI0202   216787   216440   ribosomal protein L19 (rpL19) { Escherichia coli }   89.5   98.2   114       HI0782   840039   840857   ribosomal protein L2 (rpL2) { Escherichia coli }   85.7   93.4   273       HI1323   1395432   1395782   ribosomal protein L20 (rpL20) { Escherichia coli }   94.0   96.6   117       HI0882   932097   931789   ribosomal protein L21 (rpL21) { Escherichia coli }   79.6   86.4   103       HI0784   841173   841502   ribosomal protein L22 (rpL22) { Escherichia coli }   91.8   97.3   110       HI0781   839722   840018   ribosomal protein L23 (rpL23) { Escherichia coli }   71.7   82.8   99       HI0791   844761   845069   ribosomal protein L24 (rpL24) { Escherichia coli }   76.7   86.4   103       HI1636   1692153   1692437   ribosomal protein L25 (rpL25) { Escherichia coli }   61.9   77.4   84       HI0881   931428   931788   ribosomal protein L27 (rpL27) { Escherichia coli }   87.1   90.6   85       HI0953   1010494   1010261   ribosomal protein L28 (rpL28) { Escherichia coli }   85.7   94.8   77       HI0787   842654   842842   ribosomal protein L29 (rpL29) { Escherichia coli }   75.8   87.1   62       HI0779   838481   839104   ribosomal protein L3 (rpL3) { Escherichia coli }   85.2   92.3   209       HI0798   847813   847989   ribosomal protein L30 (rpL30) { Escherichia coli }   79.7   86.4   59       HI0760   821826   821617   ribosomal protein L31 (rpL31) { Escherichia coli }   71.4   85.7   70       HI0159   174441   174274   ribosomal protein L32 (rpL32) { Escherichia coli }   77.2   86.0   57       HI0952   1010246   1010079   ribosomal protein L33 (rpL33) { Escherichia coli }   81.5   90.7   54       HI1000   1063233   1063364   ribosomal protein L34 (rpL34) { Escherichia coli }   86.4   93.2   44       HI1322   1395096   1395269   ribosomal protein L35 (rpL35) { Escherichia coli }   75.0   90.6   32       HI0780   839123   839722   ribosomal protein L4 (rpL4) { Escherichia coli }   83.6   93.0   201       HI0792   845090   845626   ribosomal protein L5 (rpL5) { Escherichia coli }   90.5   96.1   179       HI0795   846391   846921   ribosomal protein L6 (rpL6) { Escherichia coli }   75.1   90.4   177       HI0643   681915   682283   ribosomal protein L7/L12 (rpL7/L12) { Escherichia coli }   82.0   91.8   121       HI0546   567619   567173   ribosomal protein L9 (rpL9) { Escherichia coli }   72.5   85.9   149       HI1223   1289629   1291274   ribosomal protein S1 (rpS1) { Escherichia coli }   79.3   88.7   557       HI0778   838108   838461   ribosomal protein S10 (rpS10) { Escherichia coli }   98.1   99.0   103       HI0802   850416   850802   ribosomal protein S11 (rpS11) { Escherichia coli }   92.2   96.1   129       HI0801   850045   850397   ribosomal protein S13 (rpS13) { Escherichia coli }   86.4   93.2   118       HI0793   845641   845943   ribosomal protein S14 (rpS14) { Escherichia coli }   89.9   94.9   99       HI1331   1405806   1406072   ribosomal protein S15 (rpS15) { Escherichia coli }   80.9   86.5   89       HI1473   1554091   1553825   ribosomal protein S15 (rpS15) { Escherichia coli }   80.9   86.5   89       HI0205   218422   218177   ribosomal protein S16 (rpS16) { Escherichia coli }   70.7   85.4   82       HI0788   842845   843099   ribosomal protein S17 (rpS17) { Escherichia coli }   85.7   94.0   84       HI0547   567863   567639   ribosomal protein S18 (rpS18) { Escherichia coli }   92.0   94.7   75       HI0783   840886   841158   ribosomal protein S19 (rpS19) { Escherichia coli }   90.1   97.8   91       HI0915   967289   968041   ribosomal protein S2 (rpS2) { Escherichia coli }   82.2   89.2   241       HI0533   553446   553658   ribosomal protein S21 (rpS21) { Escherichia coli }   83.1   87.3   71       HI0785   841523   842227   ribosomal protein S3 (rpS3) { Escherichia coli }   87.2   93.2   233       HI0803   850833   851450   ribosomal protein S4 (rpS4) { Escherichia coli }   89.3   94.7   206       HI0797   847306   847803   ribosomal protein S5 (rpS5) { Escherichia coli }   92.8   95.8   166       HI0549   568566   568192   ribosomal protein S6 (rpS6) { Escherichia coli }   76.8   87.2   125       HI1537   1604087   1603182   ribosomal protein S6 modification protein (rimK) { Escherichia coli }   45.3   69.0   272       HI0582   599803   599336   ribosomal protein S7 (rpS7) { Escherichia coli }   89.7   94.2   155       HI0794   845983   846372   ribosomal protein S8 (rpS8) { Escherichia coli }   86.2   90.8   130       HI1446   1530328   1529939   ribosomal protein S9 (rpS9) { Haemophilus somnus }   94.6   98.5   130       HI0010   11292   10828   ribosomal-protein-alanine acetyltransferase (riml) { Escherichia coli }   55.9   73.1   144       HI0583   600334   599963   streptomycin resistance protein (strA) { Haemophilus influenzae }   100.0   100.0   124                         Amino acyl tRNA Synthetases, tRNA modification                                         HI0816   865547   862926   alanyl-tRNA synthetase (alaS) { Escherichia coli }   68.2   82.6   873       HI1589   1648685   1650415   arginyl-tRNA synthetase (argS) { Escherichia coli }   71.2   83.5   577       HI1305   1382405   1380975   asparaginyl-tRNA synthetase (asnS) { Escherichia coli }   80.6   90.8   465       HI0319   348931   347168   aspartyl-tRNA synthetase (aspS) { Escherichia coli }   76.2   85.5   585       HI0078   85367   83991   cys-tRNA synthetase (cysS) { Escherichia coli }   75.7   87.0   461       HI0710   753356   754738   cysteinyl-tRNA (ser) selenium transferase (selA) { Escherichia coli }   58.8   75.8   454       HI1357   1431798   1433466   glutaminyl-tRNA synthetase (glnS) { Escherichia coli }   75.7   86.9   547       HI0276   308282   306843   glutamyl-tRNA synthetase (gltX) { Escherichia coli }   72.4   84.3   464       HI0929   985024   984119   glycyl-tRNA synthetase alpha chain (glyQ) { Escherichia coli }   90.6   94.6   299       HI0926   983065   981002   glycyl-tRNA synthetase beta chain (glyS) { Escherichia coli }   69.7   81.9   689       HI0371   392076   393344   histidine-tRNA synthetase (hisS) { Escherichia coli }   66.8   79.1   421       HI0964   1021072   1018250   isoleucyl-tRNA ligase (ileS) { Escherichia coli }   66.0   78.5   934       HI0923   976547   979129   leucyl-tRNA synthetase (leuS) { Escherichia coli }   72.3   82.2   859       HI1214   1278435   1276930   lysyl-tRNA synthetase (lysU) { Escherichia coli }   70.2   84.3   505       HI0838   885271   886269   lysyl-tRNA synthetase analog (genX) { Escherichia coli }   62.7   78.5   331       HI0625   662613   663566   methionyl-tRNA formyltransferase (lmt) { Escherichia coli }   65.0   77.4   313       HI1279   1353301   1351256   methionyl-tRNA synthetase (metG) { Escherichia coli }   69.0   83.3   677       HI0396   416278   415697   peptidyl-tRNA hydrolase (pth) { Escherichia coli }   64.2   80.5   190       HI1314   1387690   1388676   phenylalanyl-tRNA synthetase beta-subunit (pheS) { Escherichia coli }   75.0   82.0   327       HI1315   1388713   1391097   phenylalanyl-tRNA synthetase beta-subunit (pheT) { Escherichia coli }   65.3   80.1   795       HI0731   781970   783684   prolyl-tRNA synthetase (proS) { Escherichia coli }   74.9   86.8   570       HI1650   1709685   1708879   pseudouridylate synthase I (hisT) { Escherichia coli }   69.2   82.7   260       HI0246   273589   272501   queuosine biosynthesis protein (queA) { Escherichia coli }   72.5   85.7   346       HI0201   215333   216439   selenium metabolism protein (selD) { Escherichia coli }   66.1   80.6   330       HI0110   117234   118520   seryl-tRNA synthetase (serS) { Escherichia coli }   77.6   86.5   430       HI1370   1453876   1455804   threonyl-tRNA synthetase (thrS) { Escherichia coli }   77.9   86.1   642       HI0245   272154   271009   transfer RNA-guanine transglycosylase (tgt) { Escherichia coli }   81.3   91.5   374       HI0203   217564   216827   tRNA (guanine-N1)-methyltransferase (M1G-methyltransferase) (trmD)   83.2   93.0   244                   { Escherichia coli }       HI0850   894301   895389   tRNA (uracil-5-)-methyltransferase (trmA) { Escherichia coli }   64.6   80.4   362       HI0068   71519   72451   tRNA delta(2)-isopentenylpyrophosphate transferase (trpX) { Escherichia     69.8   87.4   300                     coli }       HI1612   1671420   1672667   tRNA nucleotidyltransferase (cca) { Escherichia coli }   58.4   73.4   404       HI0242   270097   269807   tRNA-guanine-transglycosylase (tgt) { Escherichia coli }   62.4   81.7   92       HI0639   678958   677957   tryptophanyl-tRNA synthetase (trpS) { Escherichia coli }   78.1   86.2   334       HI1616   1676533   1675331   tyrosyl tRNA synthetase (tyrS) { Thiobacillus ferrooxidans }   53.6   72.6   398       HI1396   1490259   1487398   valyl-tRNA synthetase (valS) { Escherichia coli }   70.8   83.3   951                         Nucleoproteins                                         HI0187   200140   200544   DNA binding protein (probable) { Bacillus subtilis }   43.4   64.2   106       HI1496   1568461   1568685   DNA-binding protein (rdgB) { Erwinia carotovora }   42.4   60.6   67       HI1593   1655153   1655554   DNA-binding protein H-NS (hns) { Escherichia coli }   47.4   65.2   135       HI0432   453511   453104   DNA-binding protein HU-ALPHA (NS2) (HU-2) { Escherichia coli }   78.9   86.7   90                         Proteins - translation and modification                                         HI0848   893035   893757   disulfide oxidoreductase (por) { Haemophilus influenzae }   100.0   100.0   205       HI0987   1042200   1041082   DNA processing chain A (dprA) { Escherichia coli }   44.8   60.2   358       HI0916   968177   969025   elongation factor EF-Ts (tsf) { Escherichia coli }   71.4   85.0   280       HI0580   597082   595901   elongation factor EF-Tu (duplicate) (tufB) { Escherichia coli }   92.6   95.9   394       HI0634   671167   672348   elongation factor EF-Tu (duplicate) (tufB) { Escherichia coli }   92.6   95.9   394       HI0581   599249   597150   elongation factor G (fusA) { Escherichia coli }   84.6   92.0   704       HI0330   355617   355054   elongation factor P (efp) { Escherichia coli }   75.0   85.6   188       HI0069   72460   75402   glutamate-ammonia-ligase adenylyltransferase (glnE) { Escherichia coli }   52.5   69.7   914       HI1321   1394551   1394954   initiation factor 3 (infC) { Escherichia coli }   82.8   94.8   134       HI0550   569019   568768   initiation factor IF-1 (infA) { Escherichia coli }   94.4   98.6   72       HI1287   1360021   1362507   initiation factor IF-2 (infB) { Escherichia coli }   70.9   84.5   842       HI1155   1218859   1220211   maturation of antibiotic MccB17 (pmbA) { Escherichia coli }   60.8   78.7   450       HI1728   1794724   1793921   methionine aminopeptidase (map) { Escherichia coli }   64.3   79.8   262       HI0430   450570   451100   oxido-reductase (dsbB) { Escherichia coli }   43.8   68.8   174       HI1215   1279684   1278589   peptide chain release factor 2 (prfB) { Salmonella typhimurium }   81.7   93.7   365       HI1741   1811636   1813216   peptide-chain-release factor 3 (prfC) { Escherichia coli }   86.0   93.4   527       HI0079   85470   85976   peptidyl-prolyl cis-trans isomerase B (ppiB) { Escherichia coli }   71.3   80.5   163       HI1567   1631427   1630345   polypeptide chain release factor 1 (prfA) { Salmonella typhimurium }   72.5   88.3   360       HI0624   662011   662517   polypeptide deformylase (formylmethionine deformylase) (def) { Escherichia     65.1   79.9   1.69                     coli }       HI0810   857270   856716   ribosome releasing factor (frr) { Escherichia coli }   68.1   84.9   185       HI0575   593158   592940   rotamase, peptidyl prolyl cis-trans isomerase (slyD) { Escherichia coli }   50.7   73.1   67       HI0701   745982   745413   rotamase, peptidyl prolyl cis-trans isomerase (slyD) { Escherichia coli }   68.3   79.4   187       HI1334   1408450   1408923   transcription elongation factor (greA) { Escherichia coli }   79.7   89.9   158       HI0711   754738   756593   translation factor (selB) { Escherichia coli }   44.0   64.7   606       HI1216   1279817   1280503   xprA protein (xprA) { Escherichia coli }   45.4   67.4   227                         Degradation of proteins, peptides, glycopeptides                                         HI0877   927500   928801   aminopeptidase A (pepA) { Rickettsia prowazekii }   39.6   57.9   313       HI1711   1775967   1777439   aminopeptidase a/i (pepA) { Escherichia coli }   57.3   77.5   497       HI1620   1682194   1679588   aminopeptidase N (pepN) { Escherichia coli }   60.9   75.6   864       HI0818   867554   866265   aminopeptidase P (pepP) { Escherichia coli }   54.6   73.6   435       HI0716   762461   763039   ATP-dependent clp protease proteolytic component (clpP) { Escherichia coli }   71.0   88.1   193       HI0717   763052   764284   ATP-dependent protease ATPase subunit (clpX) { Escherichia coli }   70.2   83.2   413       HI0861   906379   908946   ATP-dependent protease binding subunit(clpB) { Escherichia coli }   77.4   88.6   857       HI0421   440910   442289   collagenase activity collagenase (prtC) { Porphyromonas gingivalis }   31.1   53.4   206       HI0151   166695   165811   HFLC protein (hflC) { Escherichia coli }   58.5   78.2   329       HI0248   274175   276400   IgA1 protease (iga1) { Haemophilus influenzae }   28.6   51.5   759       HI0992   1047674   1053118   IgA1 protease (iga1) { Haemophilus influenzae }   99.8   99.9   1702       HI0249   278527   276401   IgA1 protease (iga1) { Haemophilus influenzae }   45.2   62.5   791       HI1327   1402067   1403869   Ion protease (Ion) { Bacillus brevis }   24.2   46.6   714       HI0215   229004   231046   oligopeptidase A (prlC) { Escherichia coli }   72.0   84.8   678       HI0677   716670   718121   peptidase D (pepD) { Escherichia coli }   56.8   72.2   485       HI0589   608542   607865   peptidase E (pepE) { Escherichia coli }   41.4   60.0   214       HI1351   1423832   1425067   peptidase T (pepT) { Salmonella typhimurium }   53.3   71.4   398       HI1262   1336467   1335070   periplasmic serine protease Do and heat shock protein (htrA) { Escherichia     55.8   73.9   469                     coli }       HI1603   1664636   1663212   probable ATP-dependent protease (sms) { Escherichia coli }   80.0   92.2   460       HI0724   768169   768786   proline dipeptidase (pepQ) { Escherichia coli }   53.7   70.2   204       HI0137   151209   151901   protease (prtH) { Porphyromonas gingivalis }   52.6   64.9   57       HI1547   1613228   1611384   protease IV (sppA) { Escherichia coli }   43.7   64.0   607       HI1052   167927   166698   protease specific for phage lambda cll repressor (hflK) { Escherichia coli }   55.8   72.6   396       HI1688   1751031   1752089   putative protease (sohB) { Escherichia coli }   53.3   74.5   348       HI0532   553214   552189   sialoglycoprotease (gcp) { Pasteurella haemolytica }   81.8   91.5   319                 Transport/binding proteins                         Amino acids, peptides, amines                                         HI1183   1247387   1246659   arginine transport ATP-binding protein artP (artP) { Escherichia coli }   65.8   83.1   242       HI1180   1245250   1244570   arginine transport system permease protein (artM) { Escherichia coli }   55.7   79.9   218       HI1181   1245915   1245253   arginine transport system permease protein (artQ) { Escherichia coli }   59.0   77.8   229       HI0254   284235   283786   biopolymer transport protein (exbB) { Haemophilus influenzae }   96.0   98.7   150       HI0253   283779   283339   biopolymer transport protein (exbD) { Escherichia coli }   28.8   55.1   118       HI1734   1801710   1800520   branched chain aa transport system II carrier protein (braB) { Pseudomonas     28.4   49.8   279                     aeruginosa }       HI0885   935516   934149   D-alanine permease (dagA) { Alteromonas haloplanktis }   43.2   65.5   527       HI1188   1251117   1250128   dipeptide transport ATP-binding protein (dppD) { Escherichia coli }   74.2   84.0   326       HI1187   1250122   1249142   dipeptide transport ATP-binding protein (dppF) { Escherichia coli }   76.4   87.1   325       HI1126   1189626   1188709   dipeptide transport system permease protein (dppB) { Escherichia coli }   34.1   60.7   337       HI1190   1253029   1252031   dipeptide transport system permease protein (dppB) { Escherichia coli }   61.1   79.2   337       HI1189   1252013   1251130   dipeptide transport system permease protein (dppC) { Escherichia coli }   63.8   83.3   287       HI1536   1601926   1603137   glutamate permease (gltS) { Escherichia coli }   53.9   73.0   391       HI1081   1146102   1145389   glutamine transport system permease protein (glnP) { Escherichia coli }   37.6   59.0   212       HI1082   1146859   1146089   glutamine-binding periplasmic protein (glnH) { Escherichia coli }   28.4   48.2   222       HI0410   429066   428263   leucine-specific transport protein (livG) { Escherichia coli }   28.1   55.2   250       HI0227   255068   256375   membrane-associated component, LIV-II transport system (brnQ)   32.9   60.4   425                   { Salmonella typhimurium }       HI0214   228528   226987   oligopeptide binding protein (oppA) { Escherichia coli }   31.7   53.5   473       HI1127   1191333   1189710   oligopeptide binding protein (oppA) { Escherichia coli }   52.6   69.0   527       HI1124   1187751   1186783   oligopeptide transport ATP-binding protein (oppD) { Salmonella     77.2   85.0   320                     typhimurium }       HI1123   1186783   1185788   oligopeptide transport ATP-binding protein (oppF) { Salmonella typhimurium }   71.5   83.9   329       HI1125   1188696   1187764   oligopeptide transport system permease protein (oppC)C { Salmonella     71.1   87.4   300                     typhimurium }       HI1644   1702355   1704049   peptide transport periplasmic protein (sapA) { Salmonella typhimurium }   39.3   63.8   504       HI1647   1705898   1706944   peptide transport system ATP-binding protein (sapD) { Salmonella     62.4   80.0   330                     typhimurium }       HI1646   1705007   1705891   dipeptide transport system permease protein (dppC) { Escherichia coli }   36.2   59.9   279       HI1645   1704052   1705014   peptide transport system permease protein (sapB) { Salmonella     34.4   63.8   319                     typhimurium }       HI1182   1246638   1245922   periplasmic arginine-binding protein (artI) { Pasteurella haemolytica }   58.6   73.4   234       HI1157   1221270   1222589   proton glutamate symport protein (gltP) { Bacillus caldotenax }   26.6   53.6   395       HI0592   611920   610616   putrescine transport protein (potE) { Escherichia coli }   77.2   88.0   434       HI0291   324543   323308   serine transporter (sdaC) { Escherichia coli }   61.0   77.8   411       HI1350   1423563   1422421   spermidine/putrescine transport ATP-binding protein (potA) { Escherichia     68.1   83.1   378                     coli }       HI1349   1422434   1421577   spermidine/putrescine transport system permease protein (potB)   61.5   83.6   275                   { Escherichia coli }       HI1348   1421548   1420808   spermidine/putrescine transport system permease protein (potC)   72.4   88.9   243                   { Escherichia coli }       HI0500   514110   513175   spermidine/putrescine-binding periplasmic protein precursor (potD)   59.2   75.2   309                   { Escherichia coli }       HI1347   1420732   1419596   spermidine/putrescine-binding periplasmic protein precursor (potD)   54.1   71.6   330                   { Escherichia coli }       HI0289   320539   321792   tryptophan-specific permease (mtr) { Escherichia coli }   55.8   72.5   396       HI0479   497829   499028   tyrosine-specific transport protein (tyrP) { Escherichia coli }   46.1   68.2   401       HI0530   551559   550342   tyrosine-specific transport protein (tyrP) { Escherichia coli }   45.4   65.4   404                         Cations                                         HI0255   284871   284407   bacterioferritin comigratory protein (bcp) { Escherichia coli }   62.3   79.9   154       HI1275   1347862   1348650   ferric enterobactin transport ATP-binding protein (fepC) { Escherichia coli }   29.4   51.3   238       HI1475   1555193   1554435   ferric enterobactin transport ATP-binding protein (fepC) { Escherichia coli }   33.2   54.8   220       HI1471   1549654   1551853   ferrichrome-iron receptor (fhuA) { Escherichia coli }   26.4   48.9   710       HI1388   1479930   1480475   ferritin like protein (rsgA) { Escherichia coli }   57.4   79.0   162       HI1389   1480494   1480988   ferritin like protein (rsgA) { Escherichia coli }   57.3   73.8   164       HI0363   385804   384887   iron(III) dicitrate transport ATP-binding protein FECE { Escherichia coli }   35.9   56.4   220       HI1274   1347324   1347861   iron(III) dicitrate transport system permease protein (fecD) { Escherichia     36.0   64.0   255                     coli }       HI1037   1099321   1100265   magnesium and cobalt transport protein (corA) { Escherichia coli }   70.3   84.8   316       HI0097   103798   104679   major ferric iron binding protein precursor (fbp) { Neisseria gonorrhoeae }   69.7   82.3   293       HI1051   1114308   1114635   mercuric transport protein (merT) { Pseudomonas aeruginosa }   25.0   55.2   99       HI1052   1114651   1114926   mercury scavenger protein (merP) { Pseudomonas fluorescens }   29.3   45.7   91       HI0294   327396   327193   mercury scavenger protein (merP) { Psudomonas fluorescens }   32.8   67.2   67       HI1531   1594953   1594219   molybdate-binding periplasmic protein precursor (modB) { Azotobacter     21.7   43.0   245                     vinelandii }       HI0226   254880   253681   NA(+)/H(+) antiporter 1 (nhaA) { Escherichia coli }   52.6   74.6   380       HI0429   448992   450557   Na+/H+ antiporter (nhaB) { Escherichia coli }   70.6   87.5   501       HI1110   1171933   1170530   Na+/H+ antiporter (nhaC) { Bacillus firmus }   37.5   62.0   382       HI0098   104899   106317   periplasmic-binding-protein-dependent iron transport protein (sfuB)   38.1   59.5   457                   { Serratia marcescens }       HI1479   1558763   1558167   periplasmic-binding-protein-dependent iron transport protein (sfuC)   39.9   58.0   197                   { Serratia marcescens }       HI0913   964424   966276   potassium efflux system (kefC) { Escherichia coli }   40.9   65.7   594       HI0292   326934   324769   potassium/copper-transportING ATPase A (copA) { Enterococcus faecalis }   42.9   64.4   723       HI1355   1429787   1428276   sodium/proline symporter (proline permease) (putP) { Escherichia coli }   62.8   79.1   489       HI0252   283326   282517   tonB protein (tonB) { Haemophilus influenzae }   96.2   98.5   261       HI0627   664922   666362   TRK system potassium uptake protein (trkA) { Escherichia coli }   65.8   83.4   458                         Carbohydrates, organic alcohols &amp; acids                                         HI0020   22097   20661   2-oxoglutarate/malate translocator (SODiT1) { Spinacia oleracea }   35.8   59.6   452       HI0824   872894   873940   D-galactose-binding periplasmic protein (mglB) { Escherichia coli }   67.6   81.2   329       HI1113   1176024   1174516   D-xylose transport ATP-binding protein (xylG) { Escherichia coli }   71.5   85.8   501       HI1114   1177073   1176078   D-xylose-binding periplasmic protein (rbsB) { Escherichia coli }   76.0   88.4   328       HI1718   1785024   1783300   enzyme I (ptsI) { Salmonella typhimurium }   70.2   84.3   574       HI0182   194818   193967   formate transporter (formate channel) { Escherichia coli }   53.2   73.4   263       HI0450   471781   470285   fructose-permease IIA/FPR component (fruB) { Escherichia coli }   51.5   68.3   374       HI0448   469337   467670   fructose-permease IIBC component (fruA) { Escherichia coli }   57.2   72.2   552       HI0614   643282   642851   fucose operon protein (fucU) { Escherichia coli }   66.3   80.0   94       HI0692   733673   734464   glpF protein (glpF) { Escherichia coli }   73.6   87.2   258       HI1019   1080518   1081194   glpF protein (glpF) { Escherichia coli }   30.6   54.6   208       HI1017   1078404   1079867   gluconate permease (gntP) { Bacillus subtilis }   29.1   56.4   442       HI1717   1783237   1782740   glucose phosphotransferase enzyme III-glc (crr) { Escherichia coli }   73.2   83.3   169       HI0688   729474   730914   glycerol-3-phosphatase transporter (glpT) { Escherichia coli }   64.5   78.9   445       HI0504   517869   519347   high affinity ribose transport protein (rbsA) { Escherichia coli }   71.1   85.4   494       HI0505   519363   520331   high affinity ribose transport protein (rbsC) { Escherichia coli }   68.0   86.5   303       HI0503   517436   517852   high affinity ribose transport protein (rbsD) { Escherichia coli }   59.0   78.4   139       HI0612   642139   640856   L-fucose permease (fucP) { Escherichia coli }   35.6   57.9   413       HI1221   1288578   1286983   L-lactate permease (lctP) { Escherichia coli }   30.2   53.9   532       HI1735   1802527   1801757   lactam utilization protein (lamB) { Emericella nidulans }   41.3   60.3   130       HI0825   874009   875526   mglA protein (mglA) { Escherichia coli }   73.9   84.6   506       HI0826   875546   876553   mglC protein (mglC) { Escherichia coli }   79.2   90.2   336       HI0506   520354   521229   periplasmic ribose-binding protein (rbsB) { Escherichia coli }   73.9   86.6   291       HI1719   1785361   1785107   phosphohistidinoprotein-hexose phosphotransferase (ptsH) { Escherichia     77.6   88.2   85                     coli }       HI0830   878480   878773   potassium channel homolog (kch) { Escherichia coli }   67.7   80.2   96       HI0154   170140   168807   putative aspartate transport protein (dcuA) { Escherichia coli }   46.4   69.9   436       HI0748   803856   805175   putative aspartate transport protein (dcuA) { Escherichia coli }   42.6   70.1   435       HI1112   1174509   1173385   ribose transport permease protein (xylH) { Escherichia coli }   69.8   84.1   371       HI1696   1759373   1760743   sodium- and chloride-dependent GABA transporter { Homo sapiens }   29.3   52.6   471       HI0738   790926   789403   sodium-dependent noradrenaline transporter { Home sapiens }   31.1   54.2   523                         Nucleosides, purines &amp; pyrimidines                                         HI1089   1151815   1151024   ribonucleotide transport ATP-binding protein (mkl) { Mycobacterium leprae }   42.2   61.5   244       HI1230   1296319   1295078   uracil permease (uraA) { Escherichia coli }   37.2   61.6   400                         Anions                                         HI1104   1164213   1165028   cysteine synthetase (cysZ) { Escherichia coli }   53.7   76.3   190       HI1697   1761825   1760773   hydrophilic membrane-bound protein (modC) { Escherichia coli }   55.9   74.5   263       HI1698   1762501   1761815   hydrophobic membrane-bound protein (modB) { Escherichia coli }   65.9   84.8   223       HI1384   1477430   1476585   integral membrane protein (pstA) { Escherichia coli }   59.6   77.6   272       HI0356   380045   380764   nitrate transporter ATPase component (nasD) { Klebsiella pneumoniae }   34.9   57.8   254       HI1383   1475710   1476584   peripheral membrane protein B (pstB) { Escherichia coli }   77.0   86.8   256       HI1385   1478379   1477435   peripheral membrane protein C (pstC) { Escherichia coli }   57.3   78.7   300       HI1386   1479246   1478473   periplasmic phosphate-binding protein (pstS) { Escherichia coli }   49.8   67.7   256       HI1387   1479247   1479929   periplasmic phosphate-binding protein (pstS) { Escherichia coli }   63.8   75.4   69       HI1610   1669474   1670733   phosphate permease(YBR296C) { Saccharomyces cerevisiae }   35.6   60.0   551                         Other                                         HI0060   62564   60804   ATP dependent translocator homolog (msbA) { Haemophilus influenzae }   100.0   100.0   458       HI0623   653683   662010   ATP-binding protein (abc) { Escherichia coli }   74.0   86.5   200       HI1625   1686470   1686186   cystic fibrosis transmembrane conductance regulator { Bos taurus }   35.3   60.8   233       HI0855   899042   900688   heme-binding lipoprotein (dppA) { Haemophilus influenzae }   98.9   99.3   547       HI0266   295639   298353   heme-hemopexin-binding protein (hxuA) { Haemophilus influenzae }   82.1   89.5   928       HI1476   1556199   1555189   hemin permease (hemU) { Yersinia enterecolitica }   36.1   62.7   325       HI0264   291684   293852   hemin receptor precursor (hemR) { Yersinia enterocolitica }   28.5   45.9   678       HI1712   1779487   1777481   high-affinity choline transport protein (betT) { Escherichia coli }   34.7   61.6   653       HI0663   705327   703054   lactoferrin binding protein (lbpA) { Neisseria meningitidis }   30.2   47.9   763       HI0610   637954   639336   Na+/sulfate cotransporter { Rattus norvegicus }   34.4   57.8   562       HI0977   1032420   1033871   pantothenate permease (panF) { Escherichia coli }   60.2   77.9   478       HI0714   760739   757488   transferrin binding protein 1 precursor (tbp1) { Neisseria meningitidis }   29.9   48.6   894       HI0996   1059604   1056869   transferrin binding protein 1 precursor (tbp1) { Neisseria meningitidis }   51.2   69.5   885       HI1220   1286725   1283987   transferrin binding protein 1 precursor (tbp1) { Neisseria meningitidis }   28.4   46.8   902       HI0997   1061509   1059635   transferrin binding protein 2 precursor (tbp2) { Neisseria meningitidis }   39.9   54.7   692       HI0975   1029676   1030542   transferrin-binding protein (ttbA) { Actinobacillus pleuropneumoniae }   28.9   48.0   578       HI1571   1633105   1633993   transferrin-binding protein 1 (tbp1) { Neisseria meningitidis }   41.3   59.5   727       HI0637   676956   674098   transferrin-binding protein 1 (tbp2) { Neisseria gonorrhoeae }   31.6   51.7   828       HI0665   706622   708309   transport ATP-binding protein (cydD) { Escherichia coli }   26.4   54.0   561       HI1160   1226897   1225140   transport ATP-binding protein (cydD) { Escherichia coli }   50.7   73.5   588                 Cellular processes                         Chaperones                                         HI0544   565037   565324   chaperonin (groES) (mopB) { Escherichia coli }   87.5   94.8   96       HI0545   565350   566993   heat shock protein (groEL) (mopA) { Haemophilus ducreyi }   89.8   94.9   547       HI1241   1310497   1311678   heat shock protein (dnaJ) { Escherichia coli }   68.0   82.5   376       HI0104   111572   109680   heat shock protein C62.5 (htpG) { Escherichia coli }   75.4   88.3   621       HI0375   396463   394607   hsc66 protein (hsc66) { Escherichia coli }   69.2   82.0   616       HI1240   1308539   1310443   hsp70 protein (dnaK) { Escherichia coli }   78.5   88.2   638                         Cell division                                         HI0771   831200   831853   cell division ATP-binding protein (ftsE) { Escherichia coli }   64.1   78.3   216       HI1211   1275245   1274358   cell division inhibitor (sulA) { Vibrio cholerae }   33.9   55.7   116       HI1145   1210058   1211332   cell division protein (ftsA) { Escherichia coli }   52.8   74.2   420       HI1338   1410017   1412129   cell division protein (ftsH) { Escherichia coli }   75.2   87.8   624       HI1470   1549516   1548374   cell division protein (ftsH) { Escherichia coli }   77.8   88.3   369       HI1337   1409390   1410016   cell division protein (ftsJ) { Escherichia coli }   81.7   90.4   208       HI1134   1196901   1197221   cell division protein (ftsL) { Escherichia coli }   36.6   60.4   101       HI1144   1209275   1210036   cell division protein (ftsQ) { Escherichia coli }   40.6   58.5   231       HI1140   1204467   1205648   cell division protein (ftsW) { Escherichia coli }   52.3   74.9   374       HI0770   829937   831178   cell division protein (ftsY) { Escherichia coli }   66.0   81.1   497       HI1146   1211419   1212681   cell division protein (ftsZ) { Escherichia coli }   67.2   83.1   306       HI1377   1465224   1469760   cell division protein (mukB) { Escherichia coli }   61.4   77.3   1455       HI1356   1429903   1431375   cytoplasmic axial filament protein (cafA) { Escherichia coli }   71.0   86.3   488       HI0772   831866   832795   ftsX protein (ftsX) { Escherichia coli }   43.5   69.9   292       HI1067   1128511   1129221   mukB suppressor protein (smbA) { Escherichia coli }   77.4   90.2   235       HI1135   1197237   1199067   penicillin-binding protein 3 (ftsl) { Escherichia coli }   52.8   70.7   564                         Protein, peptide secretion                                         HI0016   17278   15485   GTP-binding membrane protein (lepA) { Escherichia coli }   85.6   91.0   597       HI1472   1551915   1553681   colicin V secretion ATP-binding protein (cva8) { Escherichia coli }   29.9   56.0   373       HI1008   1070885   1071397   lipoprotein signal peptidase (lspA) { Escherichia coli }   51.3   71.5   158       HI1648   1706947   1707753   peptide transport system ATP-binding protein SAPF (sapF) { Escherichia coli }   49.6   70.8   264       HI0718   764525   764842   preprotein translocase (secE) { Escherichia coli }   40.6   62.3   106       HI0800   848438   849760   preprotein translocase SECY subunit (secY) { Escherichia coli }   74.7   86.9   443       HI0241   269734   267887   protein-export membrane protein (secD) { Escherichia coli }   59.6   77.3   615       HI0240   267876   266902   protein-export membrane protein (secF) { Escherichia coli }   48.0   73.0   302       HI0447   466800   467135   protein-export membrane protein (secG) { Escherichia coli }   58.9   81.3   110       HI0745   801965   801459   protein-export protein (secB) { Escherichia coli }   56.2   80.8   145       HI0911   961135   963837   secA protein (secA) { Escherichia coli }   68.0   81.7   896       HI0015   15473   14427   signal peptidase I (lepB) { Escherichia coli }   46.3   65.1   319       HI0106   114073   112688   signal recognition particle protein (54 homolog) (fth) { Escherichia coli }   79.9   90.9   452       HI0715   761040   762335   trigger factor (tig) { Escherichia coli }   64.4   80.3   432       HI0298   330445   329756   type 4 prepilin-like protein specific leader peptidase (hopD) { Escherichia     27.2   49.0   208                     coli }       HI0299   331661   330445   xcpS protein (xcpS) { Pseudomonas putida }   29.2   56.7   396                         Detoxification                                         HI0930   985290   986813   KW20 catalase (hktE) { Haemophilus influenzae }   99.2   99.4   508       HI1090   1152892   1152248   superoxide dismutase (sodA) { Haemophilus influenzae }   99.0   99.5   209       HI1004   1065726   1067108   thiophene and furan oxidation protein (thdF) { Escherichia coli }   73.8   85.4   451                         Cell killing                                         HI0303   334801   335697   hemolysin (tlyC) { Serpulina hyodysenteriae }   36.9   57.5   252       HI1664   1723070   1723648   hemolysin, 21 kDa (hly) { Actinobacillus pleuropneumoniae }   54.5   72.4   156       HI1376   1464493   1465221   killing protein (kicA) { Escherichia coli }   69.0   83.6   222       HI1375   1463019   1464443   killing protein suppressor (kicB) { Escherichia coli }   66.9   83.0   440       HI1053   1116898   1115057   leukotoxin secretion ATP-binding protein (lktB) { Actinobacillus     34.2   55.1   512                     actinomycetemcomitans }                         Transformation                                         HI0436   456360   455674   com101A protein (comF) ( Haemophilus influenzae }   100.0   100.0   229       HI1010   1072519   1072854   competence locus E (comE1) { Bacillus subtilis }   46.7   70.0   59       HI0603   622277   622927   tfoX protein (tfoX) { Haemophilus influenzae }   99.5   99.5   217       HI0443   462729   463571   transformation gene cluster hypothetical protein (GB: M62809_1) (com)   100.0   100.0   281                   { Haemophilus influenzae }       HI0435   455595   455002   transformation gene cluster hypothetical protein (GB: M62809_10) (com)   99.5   99.5   198                   { Haemophilus influenzae }       HI0442   460047   462638   transformation gene cluster hypothetical protein (GB: M62809_2) (com)   100.0   100.0   864                   { Haemophilus influenzae }       HI0441   459948   459154   transformation gene cluster hypothetical protein (GB: M62809_3) (com)   100.0   100.0   265                   { Haemophilus influenzae }       HI0440   459150   458647   transformation gene cluster hypothetical protein (GB: M62809_4) (com)   100.0   100.0   168                   { Haemophilus influenzae }       HI0439   458647   458129   transformation gene cluster hypothetical protein (GB: M62809_5) (com)   100.0   100.0   173                   { Haemophilus influenzae }       HI0438   458129   457719   transformation gene cluster hypothetical protein (GB: M62809_6) (com)   100.0   100.0   137                   { Haemophilus influenzae }       HI0437   457706   456385   transformation gene cluster hypothetical protein (GB: M62809_7) (com)   99.8   99.8   441                   { Haemophilus influenzae }                 Other categories                         Colicin-related functions                                         HI0384   403297   402017   colicin tolerance protein (tolB) { Escherichia coli }   63.9   78.1   409       HI1209   1272281   1272769   colicin V production protein (pur regulon) (cvpA) { Escherichia coli }   64.7   79.5   156       HI0387   405650   404967   inner membrane protein (tolQ) { Escherichia coli }   68.8   83.3   221       HI0386   404892   404476   inner membrane protein (tolR) { Escherichia coli }   61.8   78.7   136       HI0385   404457   403342   outer membrane integrity protein (tolA) { Escherichia coli }   42.6   57.1   406       HI1691   1753623   1756079   outer membrane integrity protein (tolA) { Escherichia coli }   28.9   47.7   345                         Phage-related functions and prophages                                         HI1493   1566955   1567509   E16 protein (muE16) {Bacteriophage mu}   28.5   52.8   143       HI1508   1576485   1576922   G protein (muG) {Bacteriophage mu}   38.3   52.5   147       HI1574   1636594   1636181   G protein (muG) {Bacteriophage mu}   33.3   54.0   138       HI1488   1564685   1565191   gam protein {Bacteriophage mu}   57.1   73.8   168       HI0071   78159   78860   heat shock protein B253 (grpE) { Escherichia coli }   45.9   66.5   193       HI0413   432108   431836   host factor-I (HF-I) (hfq) { Escherichia coli }   90.5   97.3   74       HI1509   1577156   1578220   I protein (muI) {Bacteriophage mu}   50.0   55.4   58       HI1485   1563429   1564289   MuB protein (muB) {Bacteriophage mu}   46.4   70.4   277       HI1521   1584995   1586365   N protein (muN) {Bacteriophage mu}   31.5   52.1   452       HI1522   1586368   1587105   P protein {Bacteriophage mu}   39.5   67.3   220       HI1416   1505940   1505428   terminase subunit 1 {Bacteriophage SF6}   32.3   52.3   128       HI1483   1560600   1562660   transposase A (muA) {Bacteriophage mu}   40.6   60.1   596                         Transposon-related functions                                         HI1106   1166078   1166803   insertion sequence IS1016(V-4) hypothetical protein (GB: X58176_2)   43.6   66.7   39                   { Haemophilus influenzae }       HI1020   1081916   1081346   IS1016-V6 protein (IS1016-V6) { Haemophilus influenzae }   91.7   93.8   191       HI1332   1406795   1406150   IS1016-V6 protein (IS1016-V6) { Haemophilus influenzae }   54.7   74.7   170       HI1583   1645515   1645991   IS1016-V6 protein (IS1016-V6) { Haemophilus influenzae }   45.4   61.2   153                         Drug/analog sensitivity                                         HI0897   947919   951014   acriflavine resistance protein (acrB) { Escherichia coli }   32.7   55.0   1027       HI0302   333614   334165   ampD signalling protein (ampD) { Escherichia coli }   56.1   75.1   172       HI1245   1315822   1314629   bicyclomycin resistance protein (bcr) { Escherichia coli }   42.6   68.7   383       HI1629   1688581   1689111   mercury resistance regulatory protein (merR2) { Thiobacillus ferrooxidans }   37.7   57.5   105       HI0650   692523   691900   modulator of drug activity (mda66) { Escherichia coli }   58.1   75.4   191       HI0899   953570   952041   multidrug resistance protein (emrB) {Escharichia coli}   67.7   84.8   499       HI0900   954752   953583   multidrug resistance protein (ermA) { Escherichia coli }   46.5   66.3   389       HI0036   37441   39472   multidrug resistance protein (mdl) { Escherichia coli }   29.0   51.2   1094       HI1467   1543471   1544832   nodulation protein T (nodT) { Rhizobium leguminosarum }   20.1   46.3   390       HI0551   569189   570049   rRNA (adenosine-N6,N6)-dimethyltransferase (kagA) { Escherichia coli }   69.3   81.5   269       HI0513   527345   526362   tellurite resistance protein (tehA) { Escherichia coli }   38.9   62.0   317       HI1278   1351140   1350283   tellurite resistance protein (tehB) { Escherichia coli }   55.2   70.6   194                         Radiation sensitivity                                         HI0954   10114121   1010711   radC protein (radC) { Escherichia coli }   49.8   71.7   219                         Adaptations, atypical conditions                                         HI1532   1596570   1595143   autotrophic growth protein (aut) { Alcaligenes eutrophus }   45.0   60.9   154       HI0722   766921   767769   heat shock protein (htpX) { Escherichia coli }   66.3   82.1   288       HI1533   1596655   1597599   heat shock protein B (ibpB) { Escherichia coli }   55.9   71.2   304       HI0947   1003887   1004906   htrA-like protein (htrH) { Escherichia coli }   55.2   72.6   262       HI0903   956705   957292   invasion protein (invA) { Bartonella bacilliformis }   39.5   60.5   167       HI1550   1615090   1614485   NAD(P)H: menadione oxidoreductase { Mus musculus }   35.9   54.9   200       HI0460   479443   478505   survival protein (surA) { Escherichia coli }   33.0   58.5   424       HI0817   866160   865738   uspA protein (uspA) { Escherichia coli }   68.6   87.1   140       HI0323   350541   350774   virulence plasmid protein (vagC) { Salmonella dublin }   35.9   57.8   62       HI1254   1326770   1327090   virulence associated protein A (vapA) { Dichelobacter nodosus }   40.8   57.7   71       HI0324   350774   351175   virulence associated protein C (vapC) { Dichelobacter nodosus }   35.4   56.9   128       HI0949   1007984   1007589   virulence associated protein C (vapC) { Dichelobacter nodosus }   40.9   60.6   131       HI0452   472751   472479   virulence associated protein D (vapC) {{ Dichelobacter nodosus }   40.7   67.0   91       HI1310   1385051   1385680   virulence plasmid protein (mlgA) { Shewanella colwelliana }   23.8   56.3   124                         Undetermined                                         HI1164   1230321   1229908   15 kDa protein (P15) { Escherichia coli }   49.3   68.4   136       HI0085   89585   88593   2-hydroxyaciddehydrogenases homolog (ddh) { Zymomonas mobilis }   51.5   72.8   324       HI0462   480185   480973   beta-lactamase regulatory homolog (mazG) { Escherichia coli }   48.3   72.6   257       HI1676   1738223   1737753   conjugative transfer co-repressor (finO) { Escherichia coli }   32.5   51.9   76       HI0309   340039   340851   delta-1-pyrroline-5-carboxylate reductase (proC) { Pseudomonas aeruginoss }   44.0   60.1   267       HI1555   1620490   1619810   devA protein (devA) { Anabaena  sp.}   42.7   66.4   219       HI0558   576002   575514   devB protein (devB) { Anabaena  sp.}   32.7   51.5   166       HI1342   1415087   1415473   embryonic abundant protein, group 3 { Triticum aestivum }   33.3   50.0   102       HI0939   996457   995658   extragenic suppressor (suhB) { Escherichia coli }   64.7   80.2   258       HI0370   390960   392063   GCPE protein (protein E) (gpcE) { Escherichia coli }   88.2   93.9   362       HI0095   102616   101864   GerC2 protein (gerC2) { Bacillus subtilis }   32.9   55.2   191       HI0669   712892   711894   glpX protein (glpX) { Escherichia coli }   69.2   83.4   325       HI1015   1076616   1077389   glyoxylate-induced protein { Escherichia coli }   39.1   57.8   258       HI0499   511702   513099   hslU protein (hslU) { Escherichia coli }   80.4   90.1   443       HI0498   511230   511754   hslV protein (hstlV) { Escherichia coli }   79.8   89.0   172       HI1120   1184041   1182516   ilv-related protein { Escherichia coli }   59.7   77.0   504       HI0287   319073   317784   isochorismate synthase (entC) { Bacillus subtilis }   31.5   48.9   311       HI1624   1686217   1685567   membrane associated ATPase (cbiO) { Propionibacterium treudenreichii }   33.7   52.7   184       HI0463   481901   481029   membrane protein (lapB) { Pasteurella haemolylica }   34.2   56.0   221       HI1122   1184867   1185742   membrane protein (lapB) { Pasteurella haemolytica }   63.1   80.2   216       HI0590   608642   609874   N-carbamyl-L-amino acid amidohydrolase { Bacillus stearothermophilus }   35.9   59.2   406       HI0380   399796   398579   nitrogen fixation protein (nifS) { Anabaena  sp.}   48.2   67.0   379       HI1298   1375045   1373735   nitrogen fixation protein (nifS) { Mycobacterium leprae }   33.4   56.2   402       HI1346   1418236   1417523   nitrogen fixation protein (nifS) { Mycobacterium leprae }   38.8   58.5   186       HI0379   398591   398139   nitrogen fixation protein (nifU) { Klebsiella pneumoniae }   50.8   74.2   122       HI0167   180354   181586   nitrogen fixation protein (rnfE) { Rhodobacter capsulatus }   30.1   47.9   292       HI1692   1756087   1757160   nitrogen fixation protein (rnfE) { Rhodobacter capsulatus }   32.7   59.5   290       HI0129   143015   144800   nitrogenase C (nifC) { Clostridium pasteurianum }   27.1   52.6   248       HI1480   1559124   1558768   nitrogenase C (nifC) ( Clostridium pasteurianum }   40.9   60.2   92       HI0359   381523   382464   nmt1 protein (nmt1) { Aspergillus parasiticus }   25.6   54.7   289       HI1299   1375415   1374882   partitioning system protein (parB) {Plasmid RP4}   43.6   67.7   141       HI0224   252941   252168   rarD protein (rarD) { Escherichia coli }   26.5   53.0   230       HI0682   721733   720840   rarD protein (rarD) { Escherichia coli }   27.1   55.0   289       HI0918   970839   970249   skp protein (skp) { Pasteurella multocida }   55.5   76.4   191       HI0983   1038375   1037893   small protein (smpB) { Escherichia coli }   78.8   91.3   160       HI1598   1661468   1659882   spolllE protein (spolllE) { Coxiella burnetii }   56.1   74.5   504       HI0898   951407   952018   suppressor protein (msgA) { Escherichia coli }   30.2   56.1   254       HI1080   1145382   1144612   surfactin (sfpo) { Bacillus subtilis }   58.2   77.9   246       HI0753   811790   811296   toxR regulon (tagD) { Vibrio cholerae }   45.7   64.0   164       HI1412   1502860   1501311   traN protein (traN) {Plasmid RP4}   40.2   61.5   233       HI0666   708305   709960   transport ATP-binding protein (cydC) { Escherichia coli }   26.3   51.7   536       HI1159   1225137   1223410   transport ATP-binding protein (cydC) { Escherichia coli }   48.5   70.1   568       HI1562   1627239   1626295   vanH protein (vanH) {Transposon Tn1546}   39.7   57.1   251       HI0632   668489   669433   mucoid status locus protein (mucB) { Pseudomonas aeruginosa }   25.4   51.8   309       HI0172   183553   184785   phenolhydroxylase (ORF6) { Acinetobacter calcoaceticus }   33.0   56.9   313       HI1390   1481177   1481266   plasma protease C1 inhibitor { Home sapiens }   75.0   79.2   23                  
 
     
       
         
           
               
             
               
                 TABLE 1(b) 
               
               
                   
               
               
                   
               
               
                 KNOWN.before 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 HI0060 
                 ATP dependent translocator homolog (msbA) 
               
               
                 HI0140 
                 outer membrane protein P2 (ompP2) 
               
               
                 HI0251 
                 single-stranded DNA binding protein (ssb) 
               
               
                 HI0252 
                 tonB protein (tonB) 
               
               
                 HI0266 
                 heme-hemopexin-binding protein (hxuA) 
               
               
                 HI0351 
                 adenylate kinase (ATP-AMP transphosphorylase) (adk) 
               
               
                 HI0352 
                 hypothetical protein (SP: P24326) 
               
               
                 HI0353 
                 udp-glucose 4-epimerase (galactowaldenase) (galE) 
               
               
                 HI0354 
                 hypothetical protein (SP: P24324) 
               
               
                 HI0383 
                 PC protein (15 kd peptidoglycan-associated outer membrane lipoprotein) (pal) 
               
               
                 HI0403 
                 outer membrane protein P1 (ompP1) 
               
               
                 HI0435 
                 transformation gene cluster hypothetical protein (GB: M62809_10) (com) 
               
               
                 HI0436 
                 com101A protein (comF) 
               
               
                 HI0437 
                 transformation gene cluster hypothetical protein (GB: M62809_7) (com) 
               
               
                 HI0438 
                 transformation gene cluster hypothetical protein (GB: M62809_6) (com) 
               
               
                 HI0439 
                 transformation gene cluster hypothetical protein (GB: M62809_5) (com) 
               
               
                 HI0440 
                 transformation gene cluster hypothetical protein (GB: M62809_4) (com) 
               
               
                 HI0441 
                 transformation gene cluster hypothetical protein (GB: M62809_3) (com) 
               
               
                 HI0442 
                 transformation gene cluster hypothetical protein (GB: M62809_2) (com) 
               
               
                 HI0443 
                 transformation gene cluster hypothetical protein (GB: M62809_1) (com) 
               
               
                 HI0514 
                 Hincll endonuclease (Hincll) 
               
               
                 HI0515 
                 modification methylase Hincll (hincllM) 
               
               
                 HI0552 
                 lipooligosaccharide biosynthesis protein 
               
               
                 HI0583 
                 streptomycin resistance protein (strA) 
               
               
                 HI0602 
                 recombinase (recA) 
               
               
                 HI0603 
                 tfoX protein (tfoX) 
               
               
                 HI0606 
                 adenylate cyclase (cyaA) 
               
               
                 HI0622 
                 28 kDa membrane protein (hlpA) 
               
               
                 HI0691 
                 protein D (hpd) 
               
               
                 HI0695 
                 lipoprotein (hel) 
               
               
                 HI0820 
                 aldose 1-epimerase precursor (mutarotase) (mro) 
               
               
                 HI0821 
                 galactokinase (galK) 
               
               
                 HI0822 
                 galactose-1-phosphate uridylyltransferase (galT) 
               
               
                 HI0823 
                 galactose operon repressor (galS) 
               
               
                 HI0847 
                 hypothetical protein (GB: M94205_1) 
               
               
                 HI0848 
                 disulfide oxidoreductase (por) 
               
               
                 HI0855 
                 heme-binding lipoprotein (dppA) 
               
               
                 HI0919 
                 protective surface antigen D15 
               
               
                 HI0930 
                 KW20 catalase (hktE) 
               
               
                 HI0959 
                 cyclic AMP receptor protein (crp) 
               
               
                 HI1090 
                 superoxide dismutase (sodA) 
               
               
                 HI1167 
                 outer membrane protein P5 (ompA) 
               
               
                 HI1191 
                 DNA helicase II (uvrD) 
               
               
                 HI1397 
                 HindIII modification methyltransferase (hindIIIM) 
               
               
                 HI1398 
                 HindIII restriction endonuclease (hindIIIR) 
               
               
                 HI1402 
                 DNA polymerase III, chi subunit (holC) 
               
               
                 HI1545 
                 lic-1 operon protein (licC) 
               
               
                 HI1546 
                 lic-1 operon protein (licD) 
               
               
                 HI1585 
                 15 kd peptidoglycan-associated lipoprotein (lpp) 
               
               
                 HI1594 
                 formyltetrahydrofolate hydrolase (purU) 
               
               
                 HI1595 
                 enolpyruvylshikimatephosphatesynthase (aroA) 
               
               
                 HI1699 
                 lsg locus hypothetical protein (GB: M94855_8) 
               
               
                 HI1700 
                 lsg locus hypothetical protein (GB: M94855_7) 
               
               
                 HI1701 
                 lsg locus hypothetical protein (GB: M94855_6) 
               
               
                 HI1702 
                 lsg locus hypothetical protein (GB: M94855_5) 
               
               
                 HI1703 
                 lsg locus hypothetical protein (GB: M94855_4) 
               
               
                 HI1704 
                 lsg locus hypothetical protein (GB: M94855_3) 
               
               
                 HI1705 
                 lsg locus hypothetical protein (GB: M94855_2) 
               
               
                 HI1706 
                 lsg locus hypothetical protein (GB: M94855_1) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
               
               
                 UNKNOWNS 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 HI0003 
                 3249 
                 2464 
               
               
                   
                 HI0004 
                 3729 
                 3268 
               
               
                   
                 HI0012 
                 11778 
                 12767 
               
               
                   
                 HI0017 
                 17829 
                 17449 
               
               
                   
                 HI0019 
                 20239 
                 18819 
               
               
                   
                 HI0021 
                 23349 
                 22102 
               
               
                   
                 HI0028 
                 29582 
                 29307 
               
               
                   
                 HI0033 
                 35298 
                 34834 
               
               
                   
                 HI0034 
                 35660 
                 35355 
               
               
                   
                 HI0035 
                 37440 
                 35788 
               
               
                   
                 HI0040 
                 43059 
                 42286 
               
               
                   
                 HI0042 
                 44594 
                 43923 
               
               
                   
                 HI0043 
                 45658 
                 44597 
               
               
                   
                 HI0044 
                 46380 
                 45721 
               
               
                   
                 HI0045 
                 47261 
                 46710 
               
               
                   
                 HI0046 
                 47328 
                 47687 
               
               
                   
                 HI0050 
                 51426 
                 50224 
               
               
                   
                 HI0051 
                 51998 
                 51504 
               
               
                   
                 HI0052 
                 53023 
                 52040 
               
               
                   
                 HI0053 
                 54078 
                 53053 
               
               
                   
                 HI0056 
                 56966 
                 56256 
               
               
                   
                 HI0059 
                 60728 
                 59733 
               
               
                   
                 HI0065 
                 67839 
                 68312 
               
               
                   
                 HI0072 
                 78167 
                 77313 
               
               
                   
                 HI0073 
                 79220 
                 78879 
               
               
                   
                 HI0074 
                 79653 
                 79216 
               
               
                   
                 HI0077 
                 83046 
                 83909 
               
               
                   
                 HI0080 
                 85983 
                 86411 
               
               
                   
                 HI0081 
                 86556 
                 87341 
               
               
                   
                 HI0082 
                 87601 
                 87864 
               
               
                   
                 HI0083 
                 87882 
                 88094 
               
               
                   
                 HI0090 
                 96604 
                 97314 
               
               
                   
                 HI0091 
                 98493 
                 97360 
               
               
                   
                 HI0092 
                 99761 
                 98505 
               
               
                   
                 HI0093 
                 100989 
                 99886 
               
               
                   
                 HI0094 
                 101511 
                 101194 
               
               
                   
                 HI0096 
                 102950 
                 103522 
               
               
                   
                 HI0100 
                 107807 
                 107415 
               
               
                   
                 HI0101 
                 108091 
                 107654 
               
               
                   
                 HI0103 
                 109598 
                 109257 
               
               
                   
                 HI0105 
                 111789 
                 112625 
               
               
                   
                 HI0107 
                 114405 
                 115612 
               
               
                   
                 HI0108 
                 115744 
                 116634 
               
               
                   
                 HI0109 
                 117067 
                 116729 
               
               
                   
                 HI0112 
                 119485 
                 119847 
               
               
                   
                 HI0114 
                 122424 
                 122311 
               
               
                   
                 HI0115 
                 128606 
                 130242 
               
               
                   
                 HI0116 
                 130860 
                 130246 
               
               
                   
                 HI0117 
                 131552 
                 131800 
               
               
                   
                 HI0120 
                 134883 
                 134380 
               
               
                   
                 HI0121 
                 136357 
                 134999 
               
               
                   
                 HI0125 
                 140096 
                 141409 
               
               
                   
                 HI0126 
                 142556 
                 141573 
               
               
                   
                 HI0127 
                 142955 
                 143011 
               
               
                   
                 HI0128 
                 142718 
                 142584 
               
               
                   
                 HI0130 
                 145160 
                 144804 
               
               
                   
                 HI0131 
                 145840 
                 145136 
               
               
                   
                 HI0134 
                 147247 
                 148419 
               
               
                   
                 HI0135 
                 148422 
                 149609 
               
               
                   
                 HI0136 
                 151208 
                 149695 
               
               
                   
                 HI0144 
                 159021 
                 158125 
               
               
                   
                 HI0146 
                 160156 
                 159932 
               
               
                   
                 HI0147 
                 160966 
                 161952 
               
               
                   
                 HI0148 
                 161966 
                 163864 
               
               
                   
                 HI0149 
                 164031 
                 165167 
               
               
                   
                 HI0150 
                 165574 
                 165762 
               
               
                   
                 HI0153 
                 168744 
                 168040 
               
               
                   
                 HI0160 
                 174988 
                 174467 
               
               
                   
                 HI0163 
                 178311 
                 177715 
               
               
                   
                 HI0165 
                 179007 
                 180080 
               
               
                   
                 HI0166 
                 180130 
                 180348 
               
               
                   
                 HI0168 
                 181582 
                 182313 
               
               
                   
                 HI0169 
                 182316 
                 182567 
               
               
                   
                 HI0170 
                 182570 
                 182938 
               
               
                   
                 HI0171 
                 182945 
                 183537 
               
               
                   
                 HI0173 
                 184932 
                 185969 
               
               
                   
                 HI0174 
                 185975 
                 186232 
               
               
                   
                 HI0175 
                 186247 
                 187500 
               
               
                   
                 HI0176 
                 188281 
                 187550 
               
               
                   
                 HI0177 
                 189257 
                 188286 
               
               
                   
                 HI0178 
                 189365 
                 190150 
               
               
                   
                 HI0179 
                 190715 
                 190236 
               
               
                   
                 HI0183 
                 195295 
                 196233 
               
               
                   
                 HI0184 
                 196413 
                 197855 
               
               
                   
                 HI0185 
                 198872 
                 198048 
               
               
                   
                 HI0188 
                 200705 
                 201555 
               
               
                   
                 HI0189 
                 201568 
                 202335 
               
               
                   
                 HI0196 
                 208646 
                 208611 
               
               
                   
                 HI0199 
                 213460 
                 214224 
               
               
                   
                 HI0204 
                 218138 
                 217605 
               
               
                   
                 HI0206 
                 218715 
                 219485 
               
               
                   
                 HI0211 
                 225095 
                 225199 
               
               
                   
                 HI0218 
                 234170 
                 234697 
               
               
                   
                 HI0220 
                 238722 
                 238084 
               
               
                   
                 HI0228 
                 256953 
                 256489 
               
               
                   
                 HI0229 
                 257403 
                 257032 
               
               
                   
                 HI0231 
                 259913 
                 260854 
               
               
                   
                 HI0233 
                 262997 
                 264382 
               
               
                   
                 HI0234 
                 264390 
                 264539 
               
               
                   
                 HI0235 
                 264822 
                 264679 
               
               
                   
                 HI0236 
                 265239 
                 265033 
               
               
                   
                 HI0238 
                 265736 
                 266389 
               
               
                   
                 HI0239 
                 266350 
                 266781 
               
               
                   
                 HI0243 
                 270426 
                 270208 
               
               
                   
                 HI0244 
                 270941 
                 270426 
               
               
                   
                 HI0247 
                 274159 
                 273716 
               
               
                   
                 HI0257 
                 285979 
                 286623 
               
               
                   
                 HI0258 
                 286796 
                 286879 
               
               
                   
                 HI0259 
                 286880 
                 288054 
               
               
                   
                 HI0260 
                 288240 
                 288058 
               
               
                   
                 HI0261 
                 288839 
                 288180 
               
               
                   
                 HI0262 
                 289503 
                 288919 
               
               
                   
                 HI0267 
                 298808 
                 298450 
               
               
                   
                 HI0268 
                 298891 
                 299487 
               
               
                   
                 HI0272 
                 304213 
                 303284 
               
               
                   
                 HI0273 
                 305079 
                 304216 
               
               
                   
                 HI0277 
                 309032 
                 310684 
               
               
                   
                 HI0278 
                 311516 
                 310710 
               
               
                   
                 HI0279 
                 311998 
                 311516 
               
               
                   
                 HI0280 
                 312417 
                 312004 
               
               
                   
                 HI0281 
                 312664 
                 312371 
               
               
                   
                 HI0283 
                 315199 
                 313886 
               
               
                   
                 HI0284 
                 315200 
                 316061 
               
               
                   
                 HI0286 
                 318836 
                 319252 
               
               
                   
                 HI0293 
                 327115 
                 326912 
               
               
                   
                 HI0295 
                 327473 
                 327856 
               
               
                   
                 HI0301 
                 333498 
                 333052 
               
               
                   
                 HI0305 
                 337302 
                 338036 
               
               
                   
                 HI0306 
                 338036 
                 338593 
               
               
                   
                 HI0307 
                 338596 
                 339012 
               
               
                   
                 HI0308 
                 339973 
                 −339068 
               
               
                   
                 HI0310 
                 340854 
                 342017 
               
               
                   
                 HI0312 
                 343117 
                 343401 
               
               
                   
                 HI0313 
                 343271 
                 343092 
               
               
                   
                 HI0317 
                 346507 
                 345770 
               
               
                   
                 HI0318 
                 347143 
                 346670 
               
               
                   
                 HI0320 
                 349150 
                 349665 
               
               
                   
                 HI0321 
                 349721 
                 350002 
               
               
                   
                 HI0322 
                 349998 
                 350444 
               
               
                   
                 HI0325 
                 351245 
                 351649 
               
               
                   
                 HI0327 
                 352729 
                 354078 
               
               
                   
                 HI0328 
                 354114 
                 354374 
               
               
                   
                 HI0329 
                 354653 
                 354697 
               
               
                   
                 HI0331 
                 355655 
                 356668 
               
               
                   
                 HI0335 
                 359242 
                 360555 
               
               
                   
                 HI0338 
                 363320 
                 363910 
               
               
                   
                 HI0340 
                 364253 
                 365296 
               
               
                   
                 HI0342 
                 367615 
                 368352 
               
               
                   
                 HI0343 
                 368440 
                 368781 
               
               
                   
                 HI0344 
                 368990 
                 369516 
               
               
                   
                 HI0345 
                 369512 
                 369790 
               
               
                   
                 HI0346 
                 369815 
                 372311 
               
               
                   
                 HI0347 
                 372369 
                 373205 
               
               
                   
                 HI0348 
                 373208 
                 374068 
               
               
                   
                 HI0349 
                 374068 
                 374517 
               
               
                   
                 HI0352 
                 377303 
                 376029 
               
               
                   
                 HI0354 
                 379329 
                 378637 
               
               
                   
                 HI0355 
                 379330 
                 380044 
               
               
                   
                 HI0357 
                 380765 
                 381167 
               
               
                   
                 HI0358 
                 381227 
                 381171 
               
               
                   
                 HI0361 
                 384039 
                 383227 
               
               
                   
                 HI0365 
                 386932 
                 387009 
               
               
                   
                 HI0366 
                 387928 
                 387053 
               
               
                   
                 HI0367 
                 388154 
                 389323 
               
               
                   
                 HI0368 
                 389428 
                 389964 
               
               
                   
                 HI0369 
                 390039 
                 390947 
               
               
                   
                 HI0372 
                 393364 
                 393975 
               
               
                   
                 HI0373 
                 394223 
                 394032 
               
               
                   
                 HI0376 
                 397168 
                 396485 
               
               
                   
                 HI0377 
                 397743 
                 397222 
               
               
                   
                 HI0378 
                 398079 
                 397759 
               
               
                   
                 HI0381 
                 400309 
                 399860 
               
               
                   
                 HI0382 
                 401087 
                 400365 
               
               
                   
                 HI0388 
                 406077 
                 405670 
               
               
                   
                 HI0390 
                 408337 
                 409044 
               
               
                   
                 HI0391 
                 409072 
                 409620 
               
               
                   
                 HI0393 
                 413144 
                 412599 
               
               
                   
                 HI0394 
                 414371 
                 413637 
               
               
                   
                 HI0395 
                 415645 
                 414557 
               
               
                   
                 HI0397 
                 416445 
                 416750 
               
               
                   
                 HI0398 
                 416756 
                 417967 
               
               
                   
                 HI0400 
                 419468 
                 420118 
               
               
                   
                 HI0402 
                 421340 
                 421056 
               
               
                   
                 HI0406 
                 425499 
                 424210 
               
               
                   
                 HI0407 
                 426365 
                 425502 
               
               
                   
                 HI0414 
                 433167 
                 432202 
               
               
                   
                 HI0417 
                 437163 
                 437957 
               
               
                   
                 HI0418 
                 437953 
                 438759 
               
               
                   
                 HI0419 
                 438773 
                 439450 
               
               
                   
                 HI0420 
                 439398 
                 440738 
               
               
                   
                 HI0422 
                 442434 
                 442730 
               
               
                   
                 HI0423 
                 443077 
                 442916 
               
               
                   
                 HI0425 
                 444797 
                 445516 
               
               
                   
                 HI0426 
                 446607 
                 445555 
               
               
                   
                 HI0433 
                 454103 
                 453516 
               
               
                   
                 HI0434 
                 454932 
                 454142 
               
               
                   
                 HI0444 
                 463691 
                 464053 
               
               
                   
                 HI0451 
                 472389 
                 471856 
               
               
                   
                 HI0453 
                 472951 
                 472763 
               
               
                   
                 HI0454 
                 474321 
                 473026 
               
               
                   
                 HI0455 
                 474696 
                 474375 
               
               
                   
                 HI0456 
                 475705 
                 474926 
               
               
                   
                 HI0458 
                 477453 
                 476743 
               
               
                   
                 HI0466 
                 485905 
                 486561 
               
               
                   
                 HI0468 
                 488712 
                 487873 
               
               
                   
                 HI0469 
                 489585 
                 488725 
               
               
                   
                 HI0471 
                 491037 
                 492317 
               
               
                   
                 HI0478 
                 497647 
                 497796 
               
               
                   
                 HI0489 
                 507333 
                 506959 
               
               
                   
                 HI0490 
                 507449 
                 508048 
               
               
                   
                 HI0491 
                 508051 
                 508521 
               
               
                   
                 HI0492 
                 508274 
                 508038 
               
               
                   
                 HI0493 
                 508854 
                 509354 
               
               
                   
                 HI0494 
                 509815 
                 509856 
               
               
                   
                 HI0495 
                 509856 
                 510253 
               
               
                   
                 HI0496 
                 510797 
                 510306 
               
               
                   
                 HI0497 
                 511011 
                 510814 
               
               
                   
                 HI0502 
                 516228 
                 517265 
               
               
                   
                 HI0509 
                 523382 
                 523930 
               
               
                   
                 HI0510 
                 524561 
                 524076 
               
               
                   
                 HI0511 
                 525540 
                 524616 
               
               
                   
                 HI0512 
                 525587 
                 526303 
               
               
                   
                 HI0521 
                 542216 
                 540966 
               
               
                   
                 HI0522 
                 543103 
                 542318 
               
               
                   
                 HI0523 
                 544656 
                 543115 
               
               
                   
                 HI0524 
                 544869 
                 545522 
               
               
                   
                 HI0525 
                 546551 
                 545484 
               
               
                   
                 HI0528 
                 549859 
                 549044 
               
               
                   
                 HI0554 
                 571956 
                 572576 
               
               
                   
                 HI0556 
                 575147 
                 574608 
               
               
                   
                 HI0557 
                 575547 
                 575211 
               
               
                   
                 HI0559 
                 576210 
                 576091 
               
               
                   
                 HI0562 
                 578540 
                 580381 
               
               
                   
                 HI0563 
                 581038 
                 580382 
               
               
                   
                 HI0564 
                 581352 
                 581744 
               
               
                   
                 HI0567 
                 584110 
                 583439 
               
               
                   
                 HI0570 
                 587757 
                 587551 
               
               
                   
                 HI0572 
                 591096 
                 590482 
               
               
                   
                 HI0574 
                 592124 
                 592846 
               
               
                   
                 HI0576 
                 593256 
                 593978 
               
               
                   
                 HI0577 
                 594070 
                 594732 
               
               
                   
                 HI0578 
                 594735 
                 595112 
               
               
                   
                 HI0579 
                 595480 
                 595764 
               
               
                   
                 HI0587 
                 607340 
                 606504 
               
               
                   
                 HI0588 
                 607795 
                 607361 
               
               
                   
                 HI0591 
                 610092 
                 610508 
               
               
                   
                 HI0594 
                 614632 
                 614441 
               
               
                   
                 HI0595 
                 616556 
                 616775 
               
               
                   
                 HI0596 
                 616702 
                 615176 
               
               
                   
                 HI0599 
                 619155 
                 619970 
               
               
                   
                 HI0600 
                 620322 
                 619999 
               
               
                   
                 HI0619 
                 650498 
                 651154 
               
               
                   
                 HI0626 
                 663569 
                 664921 
               
               
                   
                 HI0628 
                 666387 
                 666770 
               
               
                   
                 HI0629 
                 666863 
                 667117 
               
               
                   
                 HI0635 
                 672600 
                 672893 
               
               
                   
                 HI0636 
                 672899 
                 673879 
               
               
                   
                 HI0638 
                 677932 
                 677645 
               
               
                   
                 HI0640 
                 679087 
                 679701 
               
               
                   
                 HI0649 
                 691619 
                 690906 
               
               
                   
                 HI0652 
                 694996 
                 694787 
               
               
                   
                 HI0655 
                 696806 
                 697567 
               
               
                   
                 HI0658 
                 699494 
                 698946 
               
               
                   
                 HI0660 
                 701972 
                 700059 
               
               
                   
                 HI0661 
                 702429 
                 702136 
               
               
                   
                 HI0662 
                 702781 
                 702425 
               
               
                   
                 HI0664 
                 706058 
                 705867 
               
               
                   
                 HI0667 
                 711078 
                 710050 
               
               
                   
                 HI0668 
                 711395 
                 711078 
               
               
                   
                 HI0670 
                 713054 
                 713269 
               
               
                   
                 HI0672 
                 713806 
                 714236 
               
               
                   
                 HI0673 
                 715017 
                 714544 
               
               
                   
                 HI0674 
                 715691 
                 714544 
               
               
                   
                 HI0675 
                 715969 
                 715694 
               
               
                   
                 HI0679 
                 719498 
                 719061 
               
               
                   
                 HI0689 
                 731017 
                 731928 
               
               
                   
                 HI0690 
                 732026 
                 732334 
               
               
                   
                 HI0696 
                 737789 
                 738508 
               
               
                   
                 HI0698 
                 743511 
                 739619 
               
               
                   
                 HI0699 
                 744964 
                 743524 
               
               
                   
                 HI0700 
                 745259 
                 744239 
               
               
                   
                 HI0702 
                 746523 
                 746065 
               
               
                   
                 HI0703 
                 746632 
                 747648 
               
               
                   
                 HI0704 
                 747649 
                 748418 
               
               
                   
                 HI0706 
                 749006 
                 749188 
               
               
                   
                 HI0708 
                 749180 
                 749148 
               
               
                   
                 HI0720 
                 765555 
                 766304 
               
               
                   
                 HI0721 
                 766361 
                 766750 
               
               
                   
                 HI0723 
                 768095 
                 767817 
               
               
                   
                 HI0725 
                 768792 
                 770060 
               
               
                   
                 HI0726 
                 776311 
                 776868 
               
               
                   
                 HI0727 
                 776875 
                 777312 
               
               
                   
                 HI0732 
                 786122 
                 783778 
               
               
                   
                 HI0733 
                 786625 
                 786245 
               
               
                   
                 HI0734 
                 786731 
                 786582 
               
               
                   
                 HI0735 
                 787647 
                 786715 
               
               
                   
                 HI0737 
                 788457 
                 789167 
               
               
                   
                 HI0742 
                 799454 
                 800908 
               
               
                   
                 HI0743 
                 801060 
                 801386 
               
               
                   
                 HI0744 
                 801027 
                 800965 
               
               
                   
                 HI0746 
                 802425 
                 801982 
               
               
                   
                 HI0755 
                 816503 
                 817648 
               
               
                   
                 HI0757 
                 819456 
                 818531 
               
               
                   
                 HI0758 
                 820676 
                 819447 
               
               
                   
                 HI0762 
                 823117 
                 823386 
               
               
                   
                 HI0763 
                 823404 
                 824474 
               
               
                   
                 HI0764 
                 825768 
                 825091 
               
               
                   
                 HI0768 
                 829290 
                 828811 
               
               
                   
                 HI0769 
                 829882 
                 829304 
               
               
                   
                 HI0774 
                 835432 
                 834092 
               
               
                   
                 HI0775 
                 836100 
                 835432 
               
               
                   
                 HI0777 
                 836970 
                 837914 
               
               
                   
                 HI0789 
                 843493 
                 844095 
               
               
                   
                 HI0808 
                 854572 
                 855375 
               
               
                   
                 HI0809 
                 856603 
                 855413 
               
               
                   
                 HI0812 
                 860092 
                 859214 
               
               
                   
                 HI0819 
                 868114 
                 867569 
               
               
                   
                 HI0827 
                 876702 
                 877433 
               
               
                   
                 HI0828 
                 877442 
                 877996 
               
               
                   
                 HI0829 
                 877999 
                 878460 
               
               
                   
                 HI0833 
                 881059 
                 881640 
               
               
                   
                 HI0839 
                 887221 
                 886541 
               
               
                   
                 HI0840 
                 887844 
                 887278 
               
               
                   
                 HI0841 
                 888779 
                 887757 
               
               
                   
                 HI0842 
                 888896 
                 889111 
               
               
                   
                 HI0843 
                 889116 
                 890870 
               
               
                   
                 HI0844 
                 891071 
                 891898 
               
               
                   
                 HI0845 
                 891925 
                 892059 
               
               
                   
                 HI0847 
                 892866 
                 893129 
               
               
                   
                 HI0849 
                 893822 
                 894164 
               
               
                   
                 HI0851 
                 895374 
                 896144 
               
               
                   
                 HI0852 
                 896141 
                 896572 
               
               
                   
                 HI0853 
                 896977 
                 897510 
               
               
                   
                 HI0854 
                 897510 
                 898898 
               
               
                   
                 HI0856 
                 900867 
                 901625 
               
               
                   
                 HI0857 
                 902112 
                 901768 
               
               
                   
                 HI0859 
                 905068 
                 905367 
               
               
                   
                 HI0860 
                 905688 
                 906248 
               
               
                   
                 HI0862 
                 909726 
                 908989 
               
               
                   
                 HI0863 
                 912130 
                 909785 
               
               
                   
                 HI0864 
                 913029 
                 912325 
               
               
                   
                 HI0866 
                 915792 
                 913945 
               
               
                   
                 HI0868 
                 918419 
                 918538 
               
               
                   
                 HI0871 
                 920692 
                 921246 
               
               
                   
                 HI0872 
                 921338 
                 921439 
               
               
                   
                 HI0873 
                 922696 
                 923613 
               
               
                   
                 HI0876 
                 927351 
                 926155 
               
               
                   
                 HI0880 
                 931427 
                 930509 
               
               
                   
                 HI0883 
                 932310 
                 933296 
               
               
                   
                 HI0884 
                 933350 
                 934084 
               
               
                   
                 HI0888 
                 938667 
                 939068 
               
               
                   
                 HI0892 
                 943690 
                 944319 
               
               
                   
                 HI0893 
                 944315 
                 944518 
               
               
                   
                 HI0904 
                 957295 
                 958086 
               
               
                   
                 HI0905 
                 957488 
                 957174 
               
               
                   
                 HI0908 
                 959765 
                 960283 
               
               
                   
                 HI0909 
                 960628 
                 960317 
               
               
                   
                 HI0910 
                 960708 
                 961007 
               
               
                   
                 HI0914 
                 966380 
                 967141 
               
               
                   
                 HI0920 
                 974685 
                 973357 
               
               
                   
                 HI0922 
                 976298 
                 975582 
               
               
                   
                 HI0927 
                 983767 
                 983405 
               
               
                   
                 HI0928 
                 984057 
                 983800 
               
               
                   
                 HI0931 
                 988229 
                 987051 
               
               
                   
                 HI0932 
                 988850 
                 988233 
               
               
                   
                 HI0933 
                 989308 
                 988826 
               
               
                   
                 HI0935 
                 991961 
                 990760 
               
               
                   
                 HI0936 
                 993112 
                 991961 
               
               
                   
                 HI0937 
                 993639 
                 993112 
               
               
                   
                 HI0938 
                 995546 
                 993642 
               
               
                   
                 HI0940 
                 996553 
                 997110 
               
               
                   
                 HI0941 
                 997170 
                 997883 
               
               
                   
                 HI0942 
                 997886 
                 998566 
               
               
                   
                 HI0943 
                 998544 
                 998846 
               
               
                   
                 HI0945 
                 1002315 
                 1002762 
               
               
                   
                 HI0950 
                 1008217 
                 1007987 
               
               
                   
                 HI0957 
                 1013246 
                 1013899 
               
               
                   
                 HI0958 
                 1013924 
                 1014091 
               
               
                   
                 HI0960 
                 1016378 
                 1015203 
               
               
                   
                 HI0961 
                 1017426 
                 1016374 
               
               
                   
                 HI0962 
                 1017780 
                 1017433 
               
               
                   
                 HI0963 
                 1018172 
                 1017783 
               
               
                   
                 HI0965 
                 1022039 
                 1021104 
               
               
                   
                 HI0966 
                 1023606 
                 1022077 
               
               
                   
                 HI0967 
                 1023993 
                 1024175 
               
               
                   
                 HI0968 
                 1024843 
                 1024944 
               
               
                   
                 HI0969 
                 1024817 
                 1024254 
               
               
                   
                 HI0976 
                 1030609 
                 1031712 
               
               
                   
                 HI0978 
                 1033994 
                 1034863 
               
               
                   
                 HI0979 
                 1034868 
                 1035440 
               
               
                   
                 HI0981 
                 1036523 
                 1037512 
               
               
                   
                 HI0986 
                 1041067 
                 1040252 
               
               
                   
                 HI0988 
                 1042709 
                 1044301 
               
               
                   
                 HI0990 
                 1045642 
                 1047047 
               
               
                   
                 HI0998 
                 1061607 
                 1062044 
               
               
                   
                 HI0999 
                 1062363 
                 1063049 
               
               
                   
                 HI1002 
                 1063710 
                 1063967 
               
               
                   
                 HI1003 
                 1063970 
                 1065592 
               
               
                   
                 HI1005 
                 1067299 
                 1067478 
               
               
                   
                 HI1006 
                 1067384 
                 1069165 
               
               
                   
                 HI1007 
                 1069256 
                 1070812 
               
               
                   
                 HI1009 
                 1071385 
                 1072338 
               
               
                   
                 HI1012 
                 1073835 
                 1074737 
               
               
                   
                 HI1013 
                 1074743 
                 1075981 
               
               
                   
                 HI1016 
                 1077448 
                 1078392 
               
               
                   
                 HI1018 
                 1079890 
                 1080315 
               
               
                   
                 HI1021 
                 1082175 
                 1083170 
               
               
                   
                 HI1022 
                 1083178 
                 1084791 
               
               
                   
                 HI1023 
                 1084736 
                 1085422 
               
               
                   
                 HI1026 
                 1089466 
                 1088792 
               
               
                   
                 HI1028 
                 1091065 
                 1090208 
               
               
                   
                 HI1029 
                 1091066 
                 1092597 
               
               
                   
                 HI1030 
                 1093581 
                 1092598 
               
               
                   
                 HI1031 
                 1094889 
                 1093615 
               
               
                   
                 HI1032 
                 1095371 
                 1094889 
               
               
                   
                 HI1033 
                 1096441 
                 1095446 
               
               
                   
                 HI1034 
                 1096617 
                 1097420 
               
               
                   
                 HI1036 
                 1098535 
                 1099023 
               
               
                   
                 HI1038 
                 1100259 
                 1100810 
               
               
                   
                 HI1039 
                 1101878 
                 1100997 
               
               
                   
                 HI1040 
                 1102257 
                 1103456 
               
               
                   
                 HI1041 
                 1103535 
                 1103386 
               
               
                   
                 HI1045 
                 1108332 
                 1107835 
               
               
                   
                 HI1046 
                 1108943 
                 1108335 
               
               
                   
                 HI1050 
                 1113198 
                 1114304 
               
               
                   
                 HI1055 
                 1117984 
                 1118322 
               
               
                   
                 HI1056 
                 1119807 
                 1118428 
               
               
                   
                 HI1057 
                 1121239 
                 1119698 
               
               
                   
                 HI1058 
                 1123210 
                 1123287 
               
               
                   
                 HI1060 
                 1123449 
                 1122868 
               
               
                   
                 HI1065 
                 1127036 
                 1126827 
               
               
                   
                 HI1066 
                 1128454 
                 1127000 
               
               
                   
                 HI1072 
                 1135049 
                 1133604 
               
               
                   
                 HI1073 
                 1135234 
                 1134995 
               
               
                   
                 HI1074 
                 1137513 
                 1135267 
               
               
                   
                 HI1075 
                 1137884 
                 1137513 
               
               
                   
                 HI1076 
                 1138337 
                 1137888 
               
               
                   
                 HI1084 
                 1148702 
                 1148448 
               
               
                   
                 HI1085 
                 1149040 
                 1148726 
               
               
                   
                 HI1086 
                 1149695 
                 1149054 
               
               
                   
                 HI1087 
                 1150228 
                 1149728 
               
               
                   
                 HI1088 
                 1151024 
                 1150242 
               
               
                   
                 HI1091 
                 1153141 
                 1153776 
               
               
                   
                 HI1092 
                 1153784 
                 1154446 
               
               
                   
                 HI1093 
                 1154507 
                 1155244 
               
               
                   
                 HI1094 
                 1155289 
                 1155489 
               
               
                   
                 HI1095 
                 1155489 
                 1156007 
               
               
                   
                 HI1096 
                 1156007 
                 1157950 
               
               
                   
                 HI1097 
                 1158092 
                 1158634 
               
               
                   
                 HI1098 
                 1158637 
                 1160013 
               
               
                   
                 HI1099 
                 1160451 
                 1160492 
               
               
                   
                 HI1100 
                 1160501 
                 1160632 
               
               
                   
                 HI1101 
                 1160637 
                 1160942 
               
               
                   
                 HI1103 
                 1164060 
                 1163077 
               
               
                   
                 HI1107 
                 1166804 
                 1168024 
               
               
                   
                 HI1121 
                 1184774 
                 1184115 
               
               
                   
                 HI1128 
                 1191629 
                 1192577 
               
               
                   
                 HI1129 
                 1193461 
                 1193234 
               
               
                   
                 HI1131 
                 1195069 
                 1195242 
               
               
                   
                 HI1132 
                 1195447 
                 1195899 
               
               
                   
                 HI1133 
                 1195933 
                 1196895 
               
               
                   
                 HI1149 
                 1215838 
                 1214972 
               
               
                   
                 HI1150 
                 1216338 
                 1215847 
               
               
                   
                 HI1151 
                 1217066 
                 1216344 
               
               
                   
                 HI1152 
                 1217588 
                 1217073 
               
               
                   
                 HI1153 
                 1218198 
                 1217572 
               
               
                   
                 HI1154 
                 1218770 
                 1218237 
               
               
                   
                 HI1156 
                 1220425 
                 1220961 
               
               
                   
                 HI1158 
                 1223159 
                 1222695 
               
               
                   
                 HI1165 
                 1231243 
                 1230773 
               
               
                   
                 HI1168 
                 1235872 
                 1236231 
               
               
                   
                 HI1171 
                 1238778 
                 1239119 
               
               
                   
                 HI1172 
                 1239729 
                 1239166 
               
               
                   
                 HI1176 
                 1242916 
                 1243383 
               
               
                   
                 HI1178 
                 1244125 
                 1244051 
               
               
                   
                 HI1179 
                 1244360 
                 1244142 
               
               
                   
                 HI1184 
                 1248098 
                 1247517 
               
               
                   
                 HI1185 
                 1248305 
                 1248859 
               
               
                   
                 HI1186 
                 1248934 
                 1249107 
               
               
                   
                 HI1193 
                 1256974 
                 1256552 
               
               
                   
                 HI1194 
                 1257654 
                 1257067 
               
               
                   
                 HI1195 
                 1257810 
                 1257950 
               
               
                   
                 HI1198 
                 1260250 
                 1261479 
               
               
                   
                 HI1201 
                 1263689 
                 1264309 
               
               
                   
                 HI1202 
                 1264360 
                 1265430 
               
               
                   
                 HI1205 
                 1267550 
                 1268050 
               
               
                   
                 HI1206 
                 1270263 
                 1268131 
               
               
                   
                 HI1208 
                 1271751 
                 1272191 
               
               
                   
                 HI1218 
                 1282515 
                 1283219 
               
               
                   
                 HI1219 
                 1283219 
                 1283904 
               
               
                   
                 HI1225 
                 1291759 
                 1292049 
               
               
                   
                 HI1226 
                 1292052 
                 1293239 
               
               
                   
                 HI1237 
                 1306218 
                 1306673 
               
               
                   
                 HI1238 
                 1307299 
                 1306835 
               
               
                   
                 HI1239 
                 1308273 
                 1307173 
               
               
                   
                 HI1243 
                 1313696 
                 1313037 
               
               
                   
                 HI1244 
                 1313794 
                 1314591 
               
               
                   
                 HI1246 
                 1316522 
                 1315827 
               
               
                   
                 HI1247 
                 1317233 
                 1316616 
               
               
                   
                 HI1249 
                 1319911 
                 1321851 
               
               
                   
                 HI1251 
                 1325506 
                 1324541 
               
               
                   
                 HI1252 
                 1326129 
                 1325512 
               
               
                   
                 HI1253 
                 1326454 
                 1326756 
               
               
                   
                 HI1255 
                 1327256 
                 1328923 
               
               
                   
                 HI1256 
                 1328946 
                 1329326 
               
               
                   
                 HI1257 
                 1329334 
                 1330392 
               
               
                   
                 HI1258 
                 1330618 
                 1330839 
               
               
                   
                 HI1259 
                 1330839 
                 1331300 
               
               
                   
                 HI1260 
                 1331300 
                 1331470 
               
               
                   
                 HI1265 
                 1339879 
                 1339148 
               
               
                   
                 HI1268 
                 1346269 
                 1345733 
               
               
                   
                 HI1269 
                 1346756 
                 1346836 
               
               
                   
                 HI1270 
                 1346624 
                 1346241 
               
               
                   
                 HI1271 
                 1346849 
                 1347025 
               
               
                   
                 HI1272 
                 1347022 
                 1347135 
               
               
                   
                 HI1273 
                 1347135 
                 1347323 
               
               
                   
                 HI1276 
                 1348650 
                 1349453 
               
               
                   
                 HI1283 
                 1356439 
                 1356654 
               
               
                   
                 HI1284 
                 1356655 
                 1357185 
               
               
                   
                 HI1285 
                 1358080 
                 1358502 
               
               
                   
                 HI1289 
                 1367227 
                 1365851 
               
               
                   
                 HI1291 
                 1369064 
                 1369447 
               
               
                   
                 HI1292 
                 1369450 
                 1370385 
               
               
                   
                 HI1294 
                 1372453 
                 1371617 
               
               
                   
                 HI1295 
                 1373365 
                 1372583 
               
               
                   
                 HI1296 
                 1373601 
                 1373359 
               
               
                   
                 HI1297 
                 1373735 
                 1373532 
               
               
                   
                 HI1300 
                 1375530 
                 1375949 
               
               
                   
                 HI1301 
                 1375971 
                 1376663 
               
               
                   
                 HI1303 
                 1378236 
                 1380176 
               
               
                   
                 HI1304 
                 1360896 
                 1380210 
               
               
                   
                 HI1309 
                 1384563 
                 1385051 
               
               
                   
                 HI1312 
                 1386755 
                 1386510 
               
               
                   
                 HI1313 
                 1386780 
                 1387538 
               
               
                   
                 HI1317 
                 1391445 
                 1391927 
               
               
                   
                 HI1318 
                 1392096 
                 1392410 
               
               
                   
                 HI1319 
                 1392802 
                 1393383 
               
               
                   
                 HI1320 
                 1393468 
                 1394280 
               
               
                   
                 HI1326 
                 1401970 
                 1401527 
               
               
                   
                 HI1329 
                 1404808 
                 1405533 
               
               
                   
                 HI1330 
                 1405533 
                 1405667 
               
               
                   
                 HI1335 
                 1409063 
                 1408968 
               
               
                   
                 HI1336 
                 1409263 
                 1408968 
               
               
                   
                 HI1340 
                 1412995 
                 1414329 
               
               
                   
                 HI1341 
                 1414391 
                 1414882 
               
               
                   
                 HI1343 
                 1416879 
                 1415557 
               
               
                   
                 HI1344 
                 1417617 
                 1417009 
               
               
                   
                 HI1345 
                 1418133 
                 1419509 
               
               
                   
                 HI1352 
                 1426116 
                 1425637 
               
               
                   
                 HI1354 
                 1428276 
                 1427314 
               
               
                   
                 HI1358 
                 1433535 
                 1433996 
               
               
                   
                 HI1367 
                 1450229 
                 1449366 
               
               
                   
                 HI1369 
                 1453591 
                 1453010 
               
               
                   
                 HI1371 
                 1458706 
                 1455929 
               
               
                   
                 HI1372 
                 1461329 
                 1458813 
               
               
                   
                 HI1378 
                 1469827 
                 1470732 
               
               
                   
                 HI1379 
                 1470738 
                 1471610 
               
               
                   
                 HI1391 
                 1481365 
                 1481808 
               
               
                   
                 HI1394 
                 1484556 
                 1485554 
               
               
                   
                 HI1399 
                 1492391 
                 1492023 
               
               
                   
                 HI1400 
                 1493035 
                 1492616 
               
               
                   
                 HI1401 
                 1493171 
                 1493004 
               
               
                   
                 HI1404 
                 1495447 
                 1496052 
               
               
                   
                 HI1405 
                 1496978 
                 1496157 
               
               
                   
                 HI1407 
                 1498433 
                 1498230 
               
               
                   
                 HI1408 
                 1499014 
                 1498469 
               
               
                   
                 HI1409 
                 1499166 
                 1499050 
               
               
                   
                 HI1410 
                 1500612 
                 1499515 
               
               
                   
                 HI1411 
                 1501029 
                 1500676 
               
               
                   
                 HI1413 
                 1503610 
                 1504026 
               
               
                   
                 HI1414 
                 1504094 
                 1502787 
               
               
                   
                 HI1415 
                 1505280 
                 1504099 
               
               
                   
                 HI1417 
                 1506471 
                 1505953 
               
               
                   
                 HI1418 
                 1506880 
                 1506602 
               
               
                   
                 HI1419 
                 1507067 
                 1506795 
               
               
                   
                 HI1421 
                 1507987 
                 1507634 
               
               
                   
                 HI1422 
                 1508392 
                 1508327 
               
               
                   
                 HI1423 
                 1509030 
                 1508428 
               
               
                   
                 HI1424 
                 1509352 
                 1509648 
               
               
                   
                 HI1425 
                 1509648 
                 1509938 
               
               
                   
                 HI1426 
                 1510250 
                 1509975 
               
               
                   
                 HI1427 
                 1510403 
                 1510975 
               
               
                   
                 HI1428 
                 1511264 
                 1511545 
               
               
                   
                 HI1431 
                 1513776 
                 1514795 
               
               
                   
                 HI1432 
                 1514998 
                 1515831 
               
               
                   
                 HI1439 
                 1521750 
                 1522223 
               
               
                   
                 HI1440 
                 1522224 
                 1525568 
               
               
                   
                 HI1441 
                 1525569 
                 1525820 
               
               
                   
                 HI1443 
                 1526752 
                 1528626 
               
               
                   
                 HI1450 
                 1533358 
                 1533038 
               
               
                   
                 HI1454 
                 1536172 
                 1536492 
               
               
                   
                 HI1455 
                 1536633 
                 1536668 
               
               
                   
                 HI1456 
                 1537150 
                 1536566 
               
               
                   
                 HI1458 
                 1538541 
                 1537903 
               
               
                   
                 HI1460 
                 1540315 
                 1539812 
               
               
                   
                 HI1462 
                 1541101 
                 1541340 
               
               
                   
                 HI1468 
                 1547394 
                 1546060 
               
               
                   
                 HI1474 
                 1554422 
                 1554078 
               
               
                   
                 HI1477 
                 1557241 
                 1556189 
               
               
                   
                 HI1481 
                 1560071 
                 1559355 
               
               
                   
                 HI1482 
                 1560378 
                 1560563 
               
               
                   
                 HI1484 
                 1562720 
                 1562989 
               
               
                   
                 HI1486 
                 1563395 
                 1562928 
               
               
                   
                 HI1487 
                 1564353 
                 1564667 
               
               
                   
                 HI1489 
                 1565191 
                 1565349 
               
               
                   
                 HI1490 
                 1565824 
                 1566042 
               
               
                   
                 HI1491 
                 1566045 
                 1566215 
               
               
                   
                 HI1492 
                 1566221 
                 1566778 
               
               
                   
                 HI1494 
                 1567509 
                 1568060 
               
               
                   
                 HI1495 
                 1568255 
                 1568467 
               
               
                   
                 HI1497 
                 1568697 
                 1569200 
               
               
                   
                 HI1498 
                 1569285 
                 1569566 
               
               
                   
                 HI1500 
                 1569836 
                 1570093 
               
               
                   
                 HI1501 
                 1570093 
                 1570344 
               
               
                   
                 HI1502 
                 1570465 
                 1570689 
               
               
                   
                 HI1503 
                 1570599 
                 1571015 
               
               
                   
                 HI1504 
                 1571343 
                 1571909 
               
               
                   
                 HI1505 
                 1571912 
                 1573435 
               
               
                   
                 HI1506 
                 1573450 
                 1575009 
               
               
                   
                 HI1507 
                 1575103 
                 1576344 
               
               
                   
                 HI1510 
                 1578223 
                 1579146 
               
               
                   
                 HI1511 
                 1579232 
                 1579486 
               
               
                   
                 HI1512 
                 1579501 
                 1579614 
               
               
                   
                 HI1513 
                 1579620 
                 1580042 
               
               
                   
                 HI1514 
                 1580012 
                 1580593 
               
               
                   
                 HI1515 
                 1580609 
                 1580797 
               
               
                   
                 HI1516 
                 1580800 
                 1582260 
               
               
                   
                 HI1517 
                 1582273 
                 1582626 
               
               
                   
                 HI1518 
                 1582642 
                 1583022 
               
               
                   
                 HI1519 
                 1583106 
                 1584998 
               
               
                   
                 HI1520 
                 1584526 
                 1584371 
               
               
                   
                 HI1523 
                 1587316 
                 1587624 
               
               
                   
                 HI1524 
                 1587664 
                 1588209 
               
               
                   
                 HI1525 
                 1588221 
                 1588625 
               
               
                   
                 HI1526 
                 1588628 
                 1589692 
               
               
                   
                 HI1527 
                 1589781 
                 1590284 
               
               
                   
                 HI1528 
                 1590287 
                 1592155 
               
               
                   
                 HI1529 
                 1592772 
                 1593659 
               
               
                   
                 HI1530 
                 1593826 
                 1593975 
               
               
                   
                 HI1540 
                 1605903 
                 1606442 
               
               
                   
                 HI1541 
                 1606426 
                 1607595 
               
               
                   
                 HI1542 
                 1607568 
                 1607912 
               
               
                   
                 HI1548 
                 1613326 
                 1613877 
               
               
                   
                 HI1549 
                 1614482 
                 1613931 
               
               
                   
                 HI1551 
                 1616455 
                 1615214 
               
               
                   
                 HI1552 
                 1616740 
                 1617159 
               
               
                   
                 HI1554 
                 1619807 
                 1618560 
               
               
                   
                 HI1558 
                 1622639 
                 1621995 
               
               
                   
                 HI1561 
                 1626292 
                 1625114 
               
               
                   
                 HI1564 
                 1628971 
                 1628171 
               
               
                   
                 HI1566 
                 1630319 
                 1629852 
               
               
                   
                 HI1568 
                 1631692 
                 1631537 
               
               
                   
                 HI1569 
                 1632481 
                 1631948 
               
               
                   
                 HI1570 
                 1632603 
                 1632517 
               
               
                   
                 HI1572 
                 1633105 
                 1633257 
               
               
                   
                 HI1575 
                 1636870 
                 1636721 
               
               
                   
                 HI1576 
                 1637376 
                 1636870 
               
               
                   
                 HI1577 
                 1637498 
                 1637439 
               
               
                   
                 HI1586 
                 1647922 
                 1647857 
               
               
                   
                 HI1587 
                 1648198 
                 1648028 
               
               
                   
                 HI1588 
                 1648605 
                 1648189 
               
               
                   
                 HI1592 
                 1654749 
                 1653193 
               
               
                   
                 HI1596 
                 1659183 
                 1657846 
               
               
                   
                 HI1597 
                 1659861 
                 1659247 
               
               
                   
                 HI1599 
                 1661605 
                 1661453 
               
               
                   
                 HI1600 
                 1662311 
                 1661643 
               
               
                   
                 HI1601 
                 1662648 
                 1662328 
               
               
                   
                 HI1604 
                 1665779 
                 1664724 
               
               
                   
                 HI1605 
                 1666807 
                 1666094 
               
               
                   
                 HI1606 
                 1667750 
                 1666800 
               
               
                   
                 HI1607 
                 1668067 
                 1667783 
               
               
                   
                 HI1608 
                 1668561 
                 1668109 
               
               
                   
                 HI1609 
                 1668769 
                 1669446 
               
               
                   
                 HI1611 
                 1670802 
                 1671410 
               
               
                   
                 HI1613 
                 1672733 
                 1673359 
               
               
                   
                 HI1614 
                 1673350 
                 1674312 
               
               
                   
                 HI1618 
                 1678855 
                 1677464 
               
               
                   
                 HI1626 
                 1686816 
                 1686316 
               
               
                   
                 HI1627 
                 1687436 
                 1686819 
               
               
                   
                 HI1628 
                 1687921 
                 1687439 
               
               
                   
                 HI1630 
                 1688617 
                 1687937 
               
               
                   
                 HI1631 
                 1689671 
                 1689177 
               
               
                   
                 HI1632 
                 1690500 
                 1690847 
               
               
                   
                 HI1633 
                 1690388 
                 1689675 
               
               
                   
                 HI1634 
                 1690881 
                 1691282 
               
               
                   
                 HI1637 
                 1693111 
                 1692542 
               
               
                   
                 HI1643 
                 1702285 
                 1700876 
               
               
                   
                 HI1649 
                 1707768 
                 1708781 
               
               
                   
                 HI1653 
                 1711982 
                 1712854 
               
               
                   
                 HI1654 
                 1712909 
                 1713433 
               
               
                   
                 HI1656 
                 1715939 
                 1716046 
               
               
                   
                 HI1657 
                 1716442 
                 1716167 
               
               
                   
                 HI1658 
                 1717744 
                 1717196 
               
               
                   
                 HI1659 
                 1718225 
                 1717860 
               
               
                   
                 HI1660 
                 1720257 
                 1719409 
               
               
                   
                 HI1661 
                 1720329 
                 1722053 
               
               
                   
                 HI1662 
                 1722056 
                 1722412 
               
               
                   
                 HI1663 
                 1722428 
                 1723010 
               
               
                   
                 HI1669 
                 1732543 
                 1731909 
               
               
                   
                 HI1670 
                 1733332 
                 1732556 
               
               
                   
                 HI1671 
                 1733482 
                 1733363 
               
               
                   
                 HI1672 
                 1733919 
                 1733539 
               
               
                   
                 HI1673 
                 1735404 
                 1733938 
               
               
                   
                 HI1675 
                 1737711 
                 1737589 
               
               
                   
                 HI1677 
                 1738407 
                 1739654 
               
               
                   
                 HI1678 
                 1739641 
                 1742283 
               
               
                   
                 HI1683 
                 1745073 
                 1745741 
               
               
                   
                 HI1685 
                 1747304 
                 1747843 
               
               
                   
                 HI1686 
                 1750100 
                 1747947 
               
               
                   
                 HI1687 
                 1750833 
                 1750171 
               
               
                   
                 HI1689 
                 1752090 
                 1753040 
               
               
                   
                 HI1690 
                 1753041 
                 1753619 
               
               
                   
                 HI1693 
                 1757163 
                 1757783 
               
               
                   
                 HI1694 
                 1757788 
                 1758492 
               
               
                   
                 HI1707 
                 1770253 
                 1770993 
               
               
                   
                 HI1709 
                 1774757 
                 1773684 
               
               
                   
                 HI1710 
                 1775859 
                 1774744 
               
               
                   
                 HI1715 
                 1782227 
                 1781865 
               
               
                   
                 HI1716 
                 1782482 
                 1782345 
               
               
                   
                 HI1720 
                 1786560 
                 1785523 
               
               
                   
                 HI1721 
                 1786631 
                 1787176 
               
               
                   
                 HI1723 
                 1788842 
                 1788747 
               
               
                   
                 HI1724 
                 1789761 
                 1788979 
               
               
                   
                 HI1726 
                 1792471 
                 1793034 
               
               
                   
                 HI1727 
                 1793205 
                 1793852 
               
               
                   
                 HI1729 
                 1794860 
                 1795201 
               
               
                   
                 HI1730 
                 1795161 
                 1795556 
               
               
                   
                 HI1736 
                 1803407 
                 1802481 
               
               
                   
                 HI1737 
                 1804045 
                 1803407 
               
               
                   
                 HI1742 
                 1813528 
                 1813298 
               
               
                   
                 HI1743 
                 1813960 
                 1813634 
               
               
                   
                 HI1744 
                 1814691 
                 1813960 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                   
               
               
                 Whole Genome Sequencing Strategy 
               
            
           
           
               
               
            
               
                 Stage 
                 Description 
               
               
                   
               
               
                 Random small insert and 
                 Randomly sheared genomic DNA on the order of 
               
               
                 large insert library construction 
                 2 kb and 15-20 kb respectively 
               
               
                 Library Plating 
                 Verify random nature of library and maximize random 
               
               
                   
                 selection of small insert and large insert clones for template 
               
               
                   
                 production 
               
               
                 High-throughput 
                 Sequence sufficient number of sequence fragments from 
               
               
                 DNA sequencing 
                 both ends for 6X coverage 
               
               
                 Assembly 
                 Assemble random sequence fragments and 
               
               
                   
                 identify repeat regions 
               
               
                 Gap closure 
               
               
                   a. Physical gaps 
                 Order all contigs (fingerprints, peptide links, 
               
               
                   
                 lambda clones, PCR) and provide templates for closure 
               
               
                   b. Sequence gaps 
                 Complete the genome sequence by primer walking 
               
               
                 Editing 
                 Visual inspection and resolution of sequence 
               
               
                   
                 ambiguities, including frameshifts 
               
               
                 Annotation 
                 Identification and description of all predicted coding 
               
               
                   
                 regions (putative identifications, starts and stops, role 
               
               
                   
                 assignments, operons, regulatory regions) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                   
               
               
                 The theory of shotgun sequencing follows from the application of the 
               
               
                 equation for the Poisson distribution p x  = m x e −m/x!  where x is the 
               
               
                 number of occurrences of an event and m is the mean number of 
               
               
                 occurrences. The numbers below predict the assembly of a 1.9 Mb 
               
               
                 genome with an average sequence fragment size of 460 bp. 
               
            
           
           
               
               
               
               
               
            
               
                   
                 % 
                 bp 
                   
                 Avg. Gap 
               
               
                 N 
                 unsequenced 
                 unsequenced 
                 DS Gaps 
                 Length 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 250 
                 94.44 
                 1794304 
                 236 
                 7600 
               
               
                 500 
                 89.18 
                 1694487 
                 446 
                 3800 
               
               
                 1,000 
                 79.54 
                 1511204 
                 795 
                 1900 
               
               
                 2,000 
                 63.26 
                 1201967 
                 1265 
                 950 
               
               
                 3,000 
                 50.32 
                 956009 
                 1509 
                 633 
               
               
                 5,000 
                 31.83 
                 604785 
                 1592 
                 380 
               
               
                 10,000 
                 10.13 
                 192508 
                 1013 
                 190 
               
               
                 15,000 
                 3.23 
                 61277 
                 484 
                 127 
               
               
                 20,000 
                 1.03 
                 19505 
                 205 
                 95 
               
               
                 25,000 
                 0.33 
                 6209 
                 82 
                 76 
               
               
                 30,000 
                 0.10 
                 1976 
                 31 
                 63 
               
               
                 50,000 
                 0.00 
                 20 
                 1 
                 38 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                   
               
               
                 Summary of features of whole genome sequencing of  H. influenzae  Rd 
               
            
           
           
               
               
            
               
                 Description 
                 Number 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Double stranded templates 
                 19,687 
                   
               
               
                 Forward sequencing reactions (M13-21 primer) 
                 19,346 
               
               
                   # Successful (%) 
                 16,240 (84%) 
               
               
                   Average edited read length 
                 485 bp 
               
               
                 Reverse sequencing reactions (M13RP1 primer) 
                 9297 
               
               
                   # Successful (%) 
                 7,744 (83%) 
               
               
                   Average edited read length 
                 444 bp 
               
               
                 Sequence fragments in random assembly 
                 24,304 
               
               
                   Total # of base pairs 
                 11,631,485 
               
               
                   # of contigs 
                 140 
               
               
                 Physical gap closure 
                 42 
               
               
                   PCR 
                 37 
               
               
                   Southern analysis 
                 15 
               
               
                   Lambda clones 
                 23 
               
               
                   Peptide links 
                 2 
               
               
                 Terminator sequencing reactions* 
                 3,102 
               
               
                   # Successful (%) 
                 2,024 (65%) 
               
               
                   Average edited read length 
                 375 bp 
               
               
                 Genome Size 
                 1,830,121 bp 
               
               
                   # of N&#39;s in sequence (%) 
                 188 (0.01%) 
               
               
                   Coordinates of proposed origin of replication 
                 602, 483-602, 764 
               
               
                   G/C content 
                 38% 
               
               
                   # of rRNA 
                 6 
               
               
                     rrnA, rrnC, rrnD (spacer region) 
                 723 bp 
               
               
                     rrnB, rrnE, rrnF (spacer region) 
                 478 bp 
               
               
                   # of tRNA genes identified 
                 54 
               
               
                 Number of Predicted Coding Regions 
                 1,749 
               
               
                   # Unassigned role (%) 
                 724 (41%) 
               
               
                     No database match 
                 384 
               
               
                     Match hypothetical proteins 
                 340 
               
               
                   # Assigned role (%) 
                 1025 (59%) 
               
               
                     Amino acid metabolism 
                 71 (6.9%) 
               
               
                     Fatty acid/phospholipid metabolism 
                 24 (2.3%) 
               
               
                     Biosynthesis of cofactors, prosthetic 
                 54 (5.3%) 
               
               
                     groups, and carriers 
               
               
                     Purines, pyrimidines, nucleosides, 
                 54 (5.3%) 
               
               
                     nucleotides 
               
               
                     Central intermediary metabolism 
                 31 (3.0%) 
               
               
                     Energy metabolism 
                 99 (9.7%) 
               
               
                     Cell envelope 
                 82 (8.0%) 
               
               
                     Regulatory functions 
                 63 (6.1%) 
               
               
                     Replication 
                 88 (8.6%) 
               
               
                     Transcription 
                 27 (2.5%) 
               
               
                     Translation 
                 146 (14.2%) 
               
               
                     Transport/binding proteins 
                 145 (14.1%) 
               
               
                     Cellular processes 
                 42 (4.1%) 
               
               
                     Other 
                 99 (9.7%) 
               
               
                   
               
               
                   *Includes gap closure, walks on rRNA repeats, and random end-sequencing of lambda clones for assembly confirmation    
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                   
               
               
                 Two component systems in  H. influenzae  Rd 
               
            
           
           
               
               
               
               
               
               
            
               
                 ID 
                 Location 
                 Best Match 
                 % ID 
                 % Sim 
                 Length (bp) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Sensors: 
                   
                   
                   
                   
                   
               
               
                 HI0221 
                 239,378 
                 arcB { E. coli } 
                 39.5 
                 63.9 
                 200 
               
               
                 HI0269 
                 299,541 
                 narQ { E. coli } 
                 38.1 
                 68.0 
                 562 
               
               
                 HI1713 
                 1,781,143 
                 basS { E. coli } 
                 27.7 
                 51.5 
                 250 
               
               
                 HI1381 
                 1,475,017 
                 phoR { E. coli } 
                 38.1 
                 61.6 
                 280 
               
               
                 Regulators: 
               
               
                 HI0728 
                 777,934 
                 narP { E. coli } 
                 59.3 
                 77.0 
                 209 
               
               
                 HI0839 
                 887,011 
                 cpxR { E. coli } 
                 51.9 
                 73.0 
                 229 
               
               
                 HI0886 
                 936,624 
                 arcA { E. coli } 
                 77.2 
                 87.8 
                 236 
               
               
                 HI1382 
                 1,475,502 
                 phoB { E. coli } 
                 52.9 
                 71.4 
                 228 
               
               
                 HI1714 
                 1,781,799 
                 basR { E. coli } 
                 43.5 
                 59.3 
                 219