bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling
Authors: Kang Joonsoo , Volkmann Ariane , Raulet David H.
Published: July 2002

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.
Insertion of Phosphoglycerine Kinase (Pgk)-Neo 5′ of Jλ1 Dramatically Enhances Vjλ1 Rearrangement
Authors: Sun Tianhe , Storb Ursula
Published: July 2002

Gene-targeted mice were generated with a loxP-neomycin resistance gene (neor) cassette inserted upstream of the Jλ1 region and replacement of the glycine 154 codon in the Cλ1 gene with a serine codon. This insertion dramatically increases Vλ1-Jλ1 recombination. Jλ1 germline transcription levels in pre-B cells and thymus cells are also greatly increased, apparently due to the strong housekeeping phosphoglycerine kinase (PGK) promoter driving the neo gene. In contrast, deletion of the neo gene causes a significant decrease in VJλ1 recombination to levels below those in normal mice. This reduction is due to the loxP site left on the chromosome which reduces the Jλ1 germline transcription in cis. Thus, the correlation between germline transcription and variable (V), diversity (D), and joining (J) recombination is not just an all or none phenomenon. Rather, the transcription efficiency is directly associated with the recombination efficiency. Furthermore, Jλ1 and Vλ1 germline transcription itself is not sufficient to lead to VJ recombination in T cells or early pre-B cells. The findings may suggest that in vivo: (a) locus and cell type–specific transactivators direct the immunoglobulin or T cell receptor loci, respectively, to a “recombination factory” in the nucleus, and (b) transcription complexes deliver V(D)J recombinase to the recombination signal sequences.
Testicular Damage by Microcirculatory Disruption and Colonization of an Immune-Privileged Site during Borrelia crocidurae Infection
Authors: Shamaei-Tousi Alireza , Collin Ola , Bergh Anders , Bergström Sven
Published: July 2002

The agent of African relapsing fever, Borrelia crocidurae, causes reversible multiple organ damage. We hypothesize that this damage is caused when the spirochete forms aggregate with erythrocytes in vivo, creating rosettes that plug the microcirculatory system. To test this hypothesis, we compared testicular microcirculation over an extended time period in two groups of rats: one experimentally inoculated with B. crocidurae, the other with the nonerythrocyte rosette–forming Borrelia hermsii. In the B. crocidurae group, erythrocyte rosettes formed during spiro-chetemia blocked precapillary blood vessels and reduced the normal pattern of microcirculatory blood flow. After spirochetemia, erythrocyte rosettes disappeared and flow was normalized. Decreased blood flow and focal vascular damage with increased permeability and interstitial bleeding adjacent to the erythrocyte microemboli induced cell death in seminiferous tubules. Interestingly, we found that B. crocidurae could penetrate the tubules and remain in the testis long after the end of spirochetemia, suggesting that the testis can serve as a reservoir for this bacteria in subsequent relapses. The group infected with B. hermsii displayed normal testicular blood flow and vasomotion at all selected time points, and suffered no testicular damage. These results confirmed our hypothesis that the erythrocyte rosettes produce vascular obstruction and are the main cause of histopathology seen in model animal and human infections.
Kinetic Analysis of Block of Open Sodium Channels by a Peptide Containing the Isoleucine, Phenylalanine, and Methionine (IFM) Motif from the Inactivation Gate
Authors: Eaholtz Galen , Zagotta William N. , Catterall William A.
Published: July 2002

We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was ∼33 μM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of ∼0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.
Viscosity methods for piecewise smooth solutions to scalar conservation laws
Authors: Tang Tao , Teng Zhen-huan
Published: July 2002

It is proved that for scalar conservation laws, if the flux function is strictly convex, and if the entropy solution is piecewise smooth with finitely many discontinuities (which includes initial central rarefaction waves, initial shocks, possible spontaneous formation of shocks in a future time and interactions of all these patterns), then the error of viscosity solution to the inviscid solution is bounded by

O
(
ϵ
|
log
⁡
ϵ
|
+
ϵ
)

O( \epsilon \vert \log \epsilon \vert + \epsilon )

in the

L
1

L^1

-norm, which is an improvement of the

O
(

ϵ

)

O( \sqrt {\epsilon })

upper bound. If neither central rarefaction waves nor spontaneous shocks occur, the error bound is improved to

O
(
ϵ
)

O(\epsilon )

.
An intractability result for multiple integration
Authors: Sloan I. , Woźniakowski H.
Published: July 2002

We prove that the problem of multiple integration in the Korobov classEα,dE_{\alpha ,d}is intractable since the number of function evaluations required to achieve a worst case error less than11is exponential in the dimension.
Derivative superconvergent points in finite element solutions of Poisson’s equation for the serendipity and intermediate families - a theoretical justification
Authors: Zhang Zhimin
Published: July 2002

Finite element derivative superconvergent points for the Poisson equation under local rectangular mesh (in the two dimensional case) and local brick mesh (in the three dimensional situation) are investigated. All superconvergent points for the finite element space of any order that is contained in the tensor-product space and contains the intermediate family can be predicted. In case of the serendipity family, the results are given for finite element spaces of order below 7. Any finite element space that contains the complete polynomial space will have at least all superconvergent points of the related serendipity family.
The Williams conjecture is false for irreducible subshifts
Authors: Kim K. , Roush F.
Published: July 2002

We prove that the Williams conjecture is false for irreducible subshifts of finite type using relative sign-gyration numbers defined between different subshifts.
Generic extensions and multiplicative bases of quantum groups at 𝐪=0
Authors: Reineke Markus
Published: July 2002

We show that the operation of taking generic extensions provides the set of isomorphism classes of representations of a quiver of Dynkin type with a monoid structure. Its monoid ring is isomorphic to the specialization at

q
=
0

q=0

of Ringel’s Hall algebra. This provides the latter algebra with a multiplicatively closed basis. Using a crystal-type basis for a two-parameter quantum group, this multiplicative basis is related to Lusztig’s canonical basis.
Completing the E. coli proteome: a database of gene products characterised since the completion of the genome sequence.
Authors: Thomas G H
Published: July 2002

A database collating research on E. coli genes whose products have been characterised subsequent to in silico predictions from the completed genome sequence.
FORESST: fold recognition from secondary structure predictions of proteins.
Authors: Di Francesco V , Munson P J , Garnier J
Published: July 2002

MOTIVATION: A method for recognizing the three-dimensional fold from the protein amino acid sequence based on a combination of hidden Markov models (HMMs) and secondary structure prediction was recently developed for proteins in the Mainly-Alpha structural class. Here, this methodology is extended to Mainly-Beta and Alpha-Beta class proteins. Compared to other fold recognition methods based on HMMs, this approach is novel in that only secondary structure information is used. Each HMM is trained from known secondary structure sequences of proteins having a similar fold. Secondary structure prediction is performed for the amino acid sequence of a query protein. The predicted fold of a query protein is the fold described by the model fitting the predicted sequence the best. RESULTS: After model cross-validation, the success rate on 44 test proteins covering the three structural classes was found to be 59%. On seven fold predictions performed prior to the publication of experimental structure, the success rate was 71%. In conclusion, this approach manages to capture important information about the fold of a protein embedded in the length and arrangement of the predicted helices, strands and coils along the polypeptide chain. When a more extensive library of HMMs representing the universe of known structural families is available (work in progress), the program will allow rapid screening of genomic databases and sequence annotation when fold similarity is not detectable from the amino acid sequence. AVAILABILITY: FORESST web server at http://absalpha.dcrt.nih.gov:8008/ for the library of HMMs of structural families used in this paper. FORESST web server at http://www.tigr.org/ for a more extensive library of HMMs (work in progress). CONTACT: valedf@tigr.org; munson@helix.nih.gov; garnier@helix.nih.gov
A proposal for a standard CORBA interface for genome maps.
Authors: Barillot E , Leser U , Lijnzaad P , Cussat-Blanc C , Jungfer K , Guyon F , Vaysseix G , Helgesen C , Rodriguez-Tom√© P
Published: July 2002

MOTIVATION: The scientific community urgently needs to standardize the exchange of biological data. This is helped by the use of a common protocol and the definition of shared data structures. We have based our standardization work on CORBA, a technology that has become a standard in the past years and allows interoperability between distributed objects. RESULTS: We have defined an IDL specification for genome maps and present it to the scientific community. We have implemented CORBA servers based on this IDL to distribute RHdb and HuGeMap maps. The IDL will co-evolve with the needs of the mapping community. AVAILABILITY: The standard IDL for genome maps is available at http:// corba.ebi.ac.uk/RHdb/EUCORBA/MapIDL.htm l. The IORs to browse maps from Infobiogen and EBI are at http://www.infobiogen.fr/services/Hugemap/IOR and http://corba.ebi.ac.uk/RHdb/EUCORBA/IOR CONTACT: manu@infobiogen.fr, tome@ebi.ac.uk
Class II MHC quantitative binding motifs derived from a large molecular database with a versatile iterative stepwise discriminant analysis meta-algorithm.
Authors: Mallios R R
Published: July 2002

MOTIVATION: The identification of T-cell epitopes can be crucial for vaccine development. An epitope is a peptide segment that binds to both a T-cell receptor and a major histocompatibility complex (MHC) molecule. Predicting which peptide segments bind MHC molecules is the first step in epitope prediction. RESULTS: An iterative stepwise discriminant analysis meta-algorithm explores a large molecular database to derive quantitative motifs for peptide binding. The applications presented here demonstrate the algorithm's versatility by producing four closely related models for HLA-DR1. Two models use an expert initial estimate and two do not; two models use amino acid residues as the only predictors and two use amino acid groupings as additional predictors. Each model correctly classifies >90% of the peptides in the database. AVAILABILITY: Software is available commercially; data are free over the Internet.
A space-efficient algorithm for aligning large genomic

sequences
Authors: Morgenstern Burkhard
Published: July 2002

Summary: In the segment-by-segment approach to sequence alignment, pairwise and multiple alignments are generated by comparing gap-free segments of the sequences under study. This method is particularly efficient in detecting local homologies, and it has been used to identify functional regions in large genomic sequences. Herein, an algorithm is outlined that calculates optimal pairwise segment-by-segment alignments in essentially linear space.

Availability: The program is available at the Bielefeld Bioinformatics Server (BiBiServ) at http://bibiserv.techfak.uni-bielefeld.de/dialign/

Contact: morgenstern@mips.biochem.mpg.de
A collection of well characterised integral membrane proteins
Authors: Möller Steffen , Kriventseva Evgenia V. , Apweiler Rolf
Published: July 2002

Summary: A collection of transmembrane proteins with annotated transmembrane regions, for which good experimental evidence exist, was created as a test or training set for algorithms to predict transmembrane regions in proteins.

Availability: ftp://ftp.ebi.ac.uk/databases/testsets/transmembrane

Contact: moeller@ebi.ac.uk
A case study in genome-level fragment assembly
Authors: Chen Ting , Skiena Steven S.
Published: July 2002

Motivation: We use the fact of two teams independently sequencing the one megabase genome of Borrelia burgdorferi as an opportunity to study the accuracy of genome-level assembly.

Results: We compare the results of three different assembly programs (PHRAP, TIGR Assembler, and STROLL) on the DNA fragments used in both the Brookhaven and TIGR sequencing projects. We also describe the algorithms and data structures used in our assembly program STROLL, which was used in the Brookhaven Borrelia project.

Availability: http://genetics.med.harvard.edu/~tchen/STROLL.

Contact: tchen@arep.med.harvard.eduand skiena@cs.sunysb.edu.
Object-oriented parsing of biological databases with Python
Authors: Ramu Chenna , Gemünd Christine , Gibson Toby J.
Published: July 2002

Motivation: While database activities in the biological area are increasing rapidly, rather little is done in the area of parsing them in a simple and object-oriented way.

Results: We present here an elegant, simple yet powerful way of parsing biological flat-file databases. We have taken EMBL, SWISSPROT and GENBANK as examples. EMBL and SWISS-PROT do not differ much in the format structure. GENBANK has a very different format structure than EMBL and SWISS-PROT. Extracting the desired fields in an entry (for example a sub-sequence with an associated feature) for later analysis is a constant need in the biological sequence-analysis community: this is illustrated with tools to make new splice-site databases. The interface to the parser is abstract in the sense that the access to all the databases is independent from their different formats, since parsing instructions are hidden.

Availability: The modules are available at http://shag.embl-heidelberg.de:8000/Biopy/

Contact: chenna@embl-heidelberg.de

Supplementary information: http://shag.embl-heidelberg.de:8000/Biopy/

* To whom correspondence should be addressed.
Profiles from structure based sequence alignment of porins can
identify β stranded integral membrane proteins
Authors: Gnanasekaran T. V. , Peri Suraj , Arockiasamy A. , Krishnaswamy S.
Published: July 2002

Supplementary information: http://gene.tn.nic.in/sk/profiles/

Contact: krishna@mrna.tn.nic.in

To whom correspondence should be addressed.
A Web interface generator for molecular biology programs in
Unix
Authors: Letondal Catherine
Published: July 2002

Motivation: Almost all users encounter problems using sequence analysis programs. Not only are they difficult to learn because of the parameters, syntax and semantic, but many are different. That is why we have developed a Web interface generator for more than 150 molecular biology command-line driven programs, including: phylogeny, gene prediction, alignment, RNA, DNA and protein analysis, motif discovery, structure analysis and database searching programs. The generator uses XML as a high-level description language of the legacy software parameters. Its aim is to provide users with the equivalent of a basic Unix environment, with program combination, customization and basic scripting through macro registration.

Results: The program has been used for three years by about 15000 users throughout the world; it has recently been installed on other sites and evaluated as a standard user interface for EMBOSS programs.

Availability: The program is freely available over the Internet at the following URL: http://www.pasteur.fr/~letondal/Pise/.

Contact: pise@pasteur.fr
Segmentation of long genomic sequences into domains with
homogeneous composition with BASIO software
Authors: Ramensky Vasily E. , Makeev Vsevolod Ju. , Roytberg Mikhail A. , Tumanyan Vladimir G.
Published: July 2002

Summary: We present a software system BASIO that allows one to segment a sequence into regions with homogeneous nucleotide composition at a desired length scale. The system can work with arbitrary alphabet and therefore can be applied to various (e.g. protein) sequences. Several sequences of complete genomes of eukaryotes are used to demonstrate the efficiency of the software.

Availability: The BASIO suite is available for non-commercial users free of charge as a set of executables and accompanying segmentation scenarios from http://www.imb.ac.ru/compbio/basio. To obtain the source code, contact the authors.

Contact: basio@imb.ac.ru; ramensky@imb.ac.ru; makeev@imb.ac.ru

* To whom correspondence should be addressed.
ORI-GENE: gene classification based on the evolutionary tree
Authors: Mizuno Hideaki , Tanaka Yoshimasa , Nakai Kenta , Sarai Akinori
Published: July 2002

Motivation: Genome projects have produced large amounts of data on the sequences of new genes whose functions are as yet unknown. The functions of new genes are usually inferred by comparing their sequences with those of known genes, but evaluation of the sequence homology of individual genes does not make the most of the available sequence information. Therefore, new methods and tools for extracting more biological information from homology searches would be advantageous.

Results: We have developed a computational tool, ORI-GENE, to analyze the results of sequence homology searches from the perspective of the evolution of selected sets of new genes. ORI-GENE has a graphical interface and accomplishes two important tasks: first, based on the output of homology searches, it identifies species with similar genes and displays their pattern of distribution on the phylogenetic tree. This function enables one to infer the way in which a given gene may have propagated among species over time. Second, from the distribution patterns, it predicts the point at which a given gene may have been first acquired (i.e. its ‘origin’), then classifies the gene on that basis. Because it makes use of available evolutionary information to show the way in which genes cluster among species, ORI-GENE should be an effective tool for the screening and classification of new genes revealed by genome analysis.

Availability: ORI-GENE is retrievable via the Internet at: http://www.rtc.riken.go.jp/jouhou/ORI-GENE.

Contact: hideaki.mizuno@roche.com; sarai@rtc.riken.go.jp

* To whom correspondence should be addressed.

4 Present address: Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 249-8530, Japan.
MOSAIC: segmenting multiple aligned DNA sequences
Authors: André Cécile , Vincens Pierre , Boisvieux Jean-François , Hazout Serge
Published: July 2002

Summary: MOSAIC is a set of tools for the segmentation of multiple aligned DNA sequences into homogeneous zones. The segmentation is based on the distribution of mutational events along the alignment. As an example, the analysis of one repeated sequence belonging to the subtelomeric regions of the yeast genome is presented.

Availability: Free access from ftp://ftp.biomath.jussieu.fr/pub/papers/MOSAIC

Contact: can@biomath.jussieu.fr

* To whom correspondence should be addressed.
Physical mapping with automatic capture of hybridization data
Authors: Hall David , Bhandarkar Suchendra M. , Arnold Jonathan , Jiang Tongzhang
Published: July 2002

Motivation: Contig maps are a type of physical map that show the native order of a set of overlapping genomic clones. Overlaps between clones can be detected by finding common sequences using a number of experimental protocols including hybridization of probes. All current mapping algorithms of which we are aware require that hybridizations be scored using a fixed number of discrete values (typically 0/1 or high/medium/low). When hybridization data is captured automatically using digital equipment, this provides the opportunity for hybridization intensities to be used in map construction. More fine-grained distinctions in the levels of hybridization may be exploited by algorithms to generate more accurate physical maps.

Results: We describe an approach to creating contig maps that uses measured hybridization intensities instead of data scored with a fixed number of discrete values. We describe and compare four algorithms for creating physical maps with hybridization intensities. Simulations using measured intensities sampled from actual data on Aspergillus nidulans indicate that using hybridization intensities rather than data that is automatically scored with respect to threshold values may yield more accurate physical maps.

Availability: All software programs described in this paper may be obtained by contacting the authors.

Contact: suchi@cs.uga.edu

* To whom correspondence should be addressed.
Flexibility of the genetic code with respect to DNA structure
Authors: Baisnée Pierre-François , Baldi Pierre , Brunak Søren , Pedersen Anders Gorm
Published: July 2002

Motivation: The primary function of DNA is to carry genetic information through the genetic code. DNA, however, contains a variety of other signals related, for instance, to reading frame, codon bias, pairwise codon bias, splice sites and transcription regulation, nucleosome positioning and DNA structure. Here we study the relationship between the genetic code and DNA structure and address two questions. First, to which degree does the degeneracy of the genetic code and the acceptable amino acid substitution patterns allow for the superimposition of DNA structural signals to protein coding sequences? Second, is the origin or evolution of the genetic code likely to have been constrained by DNA structure?

Results: We develop an index for code flexibility with respect to DNA structure. Using five different di- or tri-nucleotide models of sequence-dependent DNA structure, we show that the standard genetic code provides a fair level of flexibility at the level of broad amino acid categories. Thus the code generally allows for the superimposition of any structural signal on any protein-coding sequence, through amino acid substitution. The flexibility observed at the level of single amino acids allows only for the superimposition of punctual and loosely positioned signals to conserved amino acid sequences. The degree of flexibility of the genetic code is low or average with respect to several classes of alternative codes. This result is consistent with the view that DNA structure is not likely to have played a significant role in the origin and evolution of the genetic code.

Contact: pfbaldi@ics.uci.edu; baisnee@ics.uci.edu; brunak@cbs.dtu.dk; gorm@cbs.dtu.dk

* To whom correspondence should be addressed.
MetaFam: a unified classification of protein families. II.

Schema and query capabilities
Authors: Shoop Elizabeth , Silverstein Kevin A. T. , Johnson James E. , Retzel Ernest F.
Published: July 2002

Motivation: Protein sequence and family data is accumulating at such a rapid rate that state-of-the-art databases and interface tools are required to aid curators with their classifications. We have designed such a system, MetaFam, to facilitate the comparison and integration of public protein sequence and family data. This paper presents the global schema, integration issues, and query capabilities of MetaFam.

Results: MetaFam is an integrated data warehouse of information about protein families and their sequences. This data has been collected into a consistent global schema, and stored in an Oracle relational database. The warehouse implementation allows for quick removal of outdated data sets. In addition to the relational implementation of the primary schema, we have developed several derived tables that enable efficient access from data visualization and exploration tools. Through a series of straightforward SQL queries, we demonstrate the usefulness of this data warehouse for comparing protein family classifications and for functional assignment of new sequences.

Availability: Access to the MetaFam database is provided through a Java applet called MetaFamView, which can be run from the MetaFam web site at http://www.metafam.ahc.umn.edu/. Access to the relational data via named Oracle accounts can be arranged with the authors. Arrangements can also be made to obtain the data in Oracle ‘export dump’ format.

Contact: metafam@ahc.umn.edu

Supplementary information: The complete relational schema, integration scripts, and analysis queries are available from the authors.

* To whom correspondence should be addressed.
Genview and Gencode : a pair of programs to

test theories of genetic code evolution
Authors: Ronneberg T. Andrew , Freeland Stephen J. , Landweber Laura F.
Published: July 2002

Summary: Genview and Gencode are tools for testing the adaptive nature of a genetic code under different assumptions about patterns of genetic error and the nature of amino acid similarity. Genview provides a user friendly, point-and-click interface by which a user may reproduce and extend analysis of the adaptive properties of the standard genetic code or any of its secondary derivatives. Genview is a graphical user interface (GUI) program which runs on Linux, Unix®and Microsoft Windows®platforms and is based on the GTK\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(+\) \end{document}toolkit. Genview outputs ASCII configuration files which are interpreted by Gencode to perform an analysis. Gencode is available for the same platforms as Genview.

Availability: Online documentation can be found at http://rnaworld.princeton.edu/genview/documentation. The source code can be downloaded from http://rnaworld.princeton.edu/genview/

Contact: sfreelan@princeton.edu

* To whom correspondence should be addressed.
Limits of homology detection by pairwise sequence comparison
Authors: Spang Rainer , Vingron Martin
Published: July 2002

Motivation: Noise in database searches resulting from random sequence similarities increases as the databases expand rapidly. The noise problems are not a technical shortcoming of the database search programs, but a logical consequence of the idea of homology searches. The effect can be observed in simulation experiments.

Results: We have investigated noise levels in pairwise alignment based database searches. The noise levels of 38 releases of the SwissProt database, display perfect logarithmic growth with the total length of the databases. Clustering of real biological sequences reduces noise levels, but the effect is marginal.

Contact: rainer@stat.duke.edu; m.vingron@dkfz-heidelberg.de

2 To whom correspondence should be addressed. Pressent address: Duke University, Institute of Statistics and Decision Sciences, Box 90251 Duke University, Durham, NC 27708-0251, USA.
BioMolQuest: integrated database-based retrieval of protein

structural and functional information
Authors: Bukhman Yury V. , Skolnick Jeffrey
Published: July 2002

Motivation: Information about a particular protein or protein family is usually distributed among multiple databases and often in more than one entry in each database. Retrieval and organization of this information can be a laborious task. This task is complicated even further by the existence of alternative terms for the same concept.

Results: The PDB, SWISS-PROT, ENZYME, and CATH databases have been imported into a combined relational database, BioMolQuest. A powerful search engine has been built using this database as a back end. The search engine achieves significant improvements in query performance by automatically utilizing cross-references between the legacy databases. The results of the queries are presented in an organized, hierarchical way.

Availability: http://bioinformatics.danforthcenter.org/yury/public/home.html. Unavailable for commercial users.

Contact: skolnick@danforthcenter.org

* To whom correspondence should be addressed.
Database verification studies of SWISS-PROT and GenBank
Authors: Karp Peter D. , Paley Suzanne , Zhu Jingchun
Published: July 2002

Problem statement: We have studied the relationships among SWISS-PROT, TrEMBL, and GenBank with two goals. First is to determine whether users can reliably identify those proteins in SWISS-PROT whose functions were determined experimentally, as opposed to proteins whose functions were predicted computationally. If this information was present in reasonable quantities, it would allow researchers to decrease the propagation of incorrect function predictions during sequence annotation, and to assemble training sets for developing the next generation of sequence-analysis algorithms. Second is to assess the consistency between translated GenBank sequences and sequences in SWISS-PROT and TrEMBL.

Results: (1) Contrary to claims by the SWISS-PROT authors, we conclude that SWISS-PROT does not identify a significant number of experimentally characterized proteins. (2) SWISS-PROT is more incomplete than we expected in that version 38.0 from July 1999 lacks many proteins from the full genomes of important organisms that were sequenced years earlier. (3) Even if we combine SWISS-PROT and TrEMBL, some sequences from the full genomes are missing from the combined dataset. (4) In many cases, translated GenBank genes do not exactly match the corresponding SWISS-PROT sequences, for reasons that include missing or removed methionines, differing translation start positions, individual amino-acid differences, and inclusion of sequence data from multiple sequencing projects. For example, results show that for Escherichia coli , 80.6% of the proteins in the GenBank entry for the complete genome have identical sequence matches with SWISS-PROT/TrEMBL sequences, 13.4% have exact substring matches, and matches for 4.1% can be found using BLAST search; the remaining 2.0% of E.coli protein sequences (most of which are ORFs) have no clear matches to SWISS-PROT/TrEMBL. Although many of these differences can be explained by the complexity of the DB, and by the curation processes used to create it, the scale of the differences is notable.

Contact: pkarp@ai.sri.com

* To whom correspondence should be addressed.
SCORE: predicting the core of protein models
Authors: Deane Charlotte M. , Kaas Quentin , Blundell Tom L.
Published: July 2002

Motivation: The prediction of the regions of homology models that can be ‘restrained by’ or ‘copied from’ the basis structures is a vital step in correct model generation, because these regions are the models most accurate part. However, there is no ideal method for the identification of their limits. In most algorithms their length depends on the number of family members and definitions of secondary structure.

Results: The algorithm SCORE steps away from the conventional definitions of the core to identify from large numbers of basis structures those regions that can be considered structurally related to a target sequence. The use of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\phi},\ {\psi}\) \end{document}constraints to accurately pinpoint the regions that are conserved across a family and environmentally constrained substitution tables to extend these regions allows SCORE to rapidly (generally in under 1 s, an order of magnitude faster than methods such as MODELLER) identify and build the core of homology models from the alignments of the target sequence to the basis structures. The SCORE algorithm was used to build 114 model cores. In only two cases was the core size less than 50% of the structure and all the cores built had an RMSD of 3.7 Âor less to the target structure.

Availability: The algorithm is available upon request.

Contact: charlotte@cryst.bioc.cam.ac.uk

* To whom correspondence should be addressed.
The HIB database of annotated UniGene clusters
Authors: Geier Birgitta , Kastenmüller Gabi , Fellenberg Matthias , Mewes Hans-Werner , Morgenstern Burkhard
Published: July 2002

Summary: The HumanInfoBase (HIB) is a database of putative human gene transcripts. UniGene clusters are assembled, and the resulting consensus sequences are submitted to the PEDANT software system (Frishman,D., Albermann,K., Hani,J., Heumann,K., Metanomski,A., Zollner,A. and Mewes,H.-W., 2001, Bioinformatics , 17, 44–57) for fully automatic sequence analysis and annotation. Predicted transcripts are classified using a variety of functional and structural categories, and hyperlinks to various databases are provided for additional information. A WWW-based graphical user interface represents the assembly process as well as functionally important sites in the putative transcripts.

Availability: http://mips.gsf.de/proj/human/

Contact: morgenst@mips.gsf.de

* To whom correspondence should be addressed.
SeWeR: a customizable and integrated dynamic HTML interface to

bioinformatics services
Authors: Kumar Basu Malay
Published: July 2002

Summary: Se quence analysis using We b R esources (SeWeR) is an integrated, Dynamic HTML (DHTML) interface to commonly used bioinformatics services available on the World Wide Web. It is highly customizable, extendable, platform neutral, completely server-independent and can be hosted as a web page as well as being used as stand-alone software running within a web browser.

Availability: The web version of SeWeR can be freely accessed from http://www.bioinformatics.org/sewer/ or http://iubio.bio.indiana.edu/webapps/SeWeR/, and also from several mirror sites all over the world (a full listing is available on the SeWeR web page).It can also be downloaded under GNU General Public License from ftp://iubio.bio.indiana.edu/molbio/analyze/sewer.zip.

Contact: curiouser@ccmb.ap.nic.in
Identifying the 3′-terminal exon in

human DNA
Authors: Tabaska Jack E. , Davuluri Ramana V. , Zhang Michael Q.
Published: July 2002

Motivation: We present JTEF, a new program for finding 3′ terminal exons in human DNA sequences. This program is based on quadratic discriminant analysis, a standard non-linear statistical pattern recognition method. The quadratic discriminant functions used for building the algorithm were trained on a set of 3′ terminal exons of type 3tuexon (those containing the true STOP codon).

Results: We showed that the average predictive accuracy of JTEF is higher than the presently available best programs (GenScan and Genemark.hmm) based on a test set of 65 human DNA sequences with 121 genes. In particular JTEF performs well on larger genomic contigs containing multiple genes and significant amounts of intergenic DNA. It will become a valuable tool for genome annotation and gene functional studies.

Availability: JTEF is available free for academic users on request from ftp://cshl.org/pub/science/mzhanglab/JTEF and will be made available through the World Wide Web (http://argon.cshl.org/).

Contact: mzhang@cshl.org; ramana@cshl.org

* To whom correspondence should be addressed.

2 Present address: Monsanto Company, 800 North Lindbergh, St Louis, MO 63167, USA.
Genotype transposer: automated genotype manipulation for
linkage disequilibrium analysis
Authors: Cox David G. , Canzian Federico
Published: July 2002

Summary: The purpose of this work is to provide the modern molecular geneticist with tools to perform more efficient and more accurate analysis of the genotype data they produce. By using Microsoft Excel macros written in Visual Basic, we can translate genotype data into a form readable by the versatile software ‘Arlequin’, read the Arlequin output, calculate statistics of linkage disequilibrium, and put the results in a format for viewing with the software ‘GOLD’.

Availability: The software is available by FTP at: ftp://xcsg.iarc.fr/cox/Genotype_Transposer/.

Contact: cox@iarc.fr

Supplementary information: Detailed instruction and examples are available at: ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at: http://lgb.unige.ch/arlequin/. GOLD is available at: http://www.well.ox.ac.uk/asthma/GOLD/.

* To whom correspondence should be addressed.
DBAli: a database of protein structure alignments
Authors: Martı́-Renom Marc
A. , Ilyin Valentin A. , Sali Andrej
Published: July 2002

Summary: The DBAli database includes approximately 35000 alignments of pairs of protein structures from SCOP (Lo Conte et al. , Nucleic Acids Res. , 28, 257–259, 2000) and CE (Shindyalov and Bourne, Protein Eng. , 11, 739–747, 1998). DBAli is linked to several resources, including Compare3D (Shindyalov and Bourne, http://www.sdsc.edu/pb/software.htm, 1999) and ModView (Ilyin and Sali, http://guitar.rockefeller.edu/ModView/, 2001) for visualizing sequence alignments and structure superpositions. A flexible search of DBAli by protein sequence and structure properties allows construction of subsets of alignments suitable for a number of applications, such as benchmarking of sequence–sequence and sequence–structure alignment methods under a variety of conditions.

Availability: http://guitar.rockefeller.edu/DBAli/

Contact: sali@rockefeller.edu; http://guitar.rockefeller.edu

* To whom correspondence should be addressed.
PathFinder: reconstruction and dynamic visualization of
metabolic pathways
Authors: Goesmann Alexander , Haubrock Martin , Meyer Folker , Kalinowski Jörn , Giegerich Robert
Published: July 2002

Motivation: Beyond methods for a gene-wise annotation and analysis of sequenced genomes new automated methods for functional analysis on a higher level are needed. The identification of realized metabolic pathways provides valuable information on gene expression and regulation. Detection of incomplete pathways helps to improve a constantly evolving genome annotation or discover alternative biochemical pathways. To utilize automated genome analysis on the level of metabolic pathways new methods for the dynamic representation and visualization of pathways are needed.

Results: PathFinder is a tool for the dynamic visualization of metabolic pathways based on annotation data. Pathways are represented as directed acyclic graphs, graph layout algorithms accomplish the dynamic drawing and visualization of the metabolic maps. A more detailed analysis of the input data on the level of biochemical pathways helps to identify genes and detect improper parts of annotations. As an Relational Database Management System (RDBMS) based internet application PathFinder reads a list of EC-numbers or a given annotation in EMBL- or Genbank-format and dynamically generates pathway graphs.

Availability: The software PathFinder will be made available on the Bielefeld Bioinformatics WebServer under the following URL: http://bibiserv.TechFak.Uni-Bielefeld.DE/pathfinder/. The source code is available upon request and will eventually be released under GPL.

Contact: Alexander.Goesmann@Genetik.Uni-Bielefeld.DE
Using biplots to interpret gene expression patterns in plants
Authors: Chapman Scott , Schenk Peer , Kazan Kemal , Manners John
Published: July 2002

Summary: Plant biologists in fields of ecology, evolution, genetics and breeding frequently use multivariate methods. This paper illustrates Principal Component Analysis (PCA) and Gabriel’s biplot as applied to microarray expression data from plant pathology experiments.

Availability: An example program in the publicly distributed statistical language R is available from the web site (www.tpp.uq.edu.au) and by e-mail from the contact.

Contact: scott.chapman@csiro.au
CIT: identification of differentially expressed clusters of
genes from microarray data
Authors: Rhodes Daniel R. , Miller Jeremy C. , Haab Brian B. , Furge Kyle A.
Published: July 2002

Summary: Cluster Identification Tool (CIT) is a microarray analysis program that identifies differentially expressed genes. Following division of experimental samples based on a parameter of interest, CIT uses a statistical discrimination metric and permutation analysis to identify clusters of genes or individual genes that best differentiate between the experimental groups. CIT integrates with the freely available CLUSTER and TREEVIEW programs to form a more complete microarray analysis package.

Availability: A Windows® binary executable is freely available at http://www.vai.org/vari/bioinformatics.htm

Contact: Kyle.Furge@vai.org

Supplementary information: http://www.vai.org/vari/bioinfomatics.htm

* To whom correspondence should be addressed.
ISEApeaks: an Excel platform for GeneScan and Immunoscope data
retrieval, management and analysis
Authors: Collette A. , Six A.
Published: July 2002

Summary: ISEApeaks retrieves and handles DNA sequencer raw data (peak area and nucleotidic length). This Macintosh package efficiently interfaces GeneScan and Immunoscope softwares to Excel by extracting data from scattered files, organizing data and gathering it into a unique peak database for all samples.

Availability: ISEApeaks is available upon request from the authors.

Contact: collette@pasteur.fr; askc@pasteur.fr, http://www.pasteur.fr/recherche/unites/Imchan/iseapeakuk.html

* To whom correspondence should be addressed.
Interactive InterPro-based comparisons of proteins in whole
genomes
Authors: Kanapin A. , Apweiler R. , Biswas M. , Fleischmann W. , Karavidopoulou Y. , Kersey P. , Kriventseva E. V. , Mittard V. , Mulder N. , Oinn T. , Phan I. , Servant F. , Zdobnov E.
Published: July 2002

Motivation: The SWISS-PROT group at the EBI has developed the Proteome Analysis Database utilizing existing resources and providing comprehensive and integrated comparative analysis of the predicted protein coding sequencesof the complete genomes of bacteria, archaea and eukaryotes. The Proteome Analysis Database is accompanied by a program that has been designed to carry out interactive InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Availability: http://www.ebi.ac.uk/proteome/comparisons.html

Contact: alex@ebi.ac.uk; proteome@ebi.ac.uk

* To whom all correspondence should be addressed.
GeneANOVA—gene expression analysis of variance
Authors: Didier G. , Brézellec P. , Remy E. , Hénaut A.
Published: July 2002

Summary: GeneANOVA is an ANOVA-based software devoted to the analysis of gene expression data.

Availability: GeneANOVA is freely available on request for non-commercial use.

Contact: didier@genopole.cnrs.fr
Gene structure identification with MyGV using cDNA
evidence and protein homologs to improve ab initio
predictions
Authors: Zhu Wei , Brendel Volker
Published: July 2002

Summary: MyGV is an application to visualize (potentially genome-scale) gene structure annotation and prediction. The output of any external gene prediction program can be easily converted to a generalized format for input into MyGV. The application displays all input simultaneously in graphical representation, with a toggle option for a text-based view. Zooming capabilities allow detailed comparisons for specific genome locations. The tool is particularly helpful for refinement of ab initio predicted gene structures by spliced alignment with cDNA or protein homologs.

Availability: The program was written in Java and is freely available to non-commercial users by electronic download from http://bioinformatics.iastate.edu/bioinformatics2go/MyGV.

Contact: vbrendel@iastate.edu
GP3: GenePix post-processing program for automated analysis of raw microarray data
Authors: Fielden M. R. , Halgren R. G. , Dere E. , Zacharewski T. R.
Published: July 2002

Summary: Here we describe an automated and customizable program to correct, filter and normalize raw microarray data captured using GenePix, a commonly used microarray image analysis application. Files can be processed individually or in batch mode for increased throughput. User defined inputs specify the stringency of data filtering and the method and conditions of normalization. The output includes gene summaries for replicate spots and descriptive statistics for each experiment. The source code (Perl) can also be adapted to handle raw data output from other image analysis applications.

Availability: http://bch.msu.edu/~zacharet/microarray/GP3.html

Contact: tzachare@msu.edu

Supplementary information: http://bch.msu.edu/~zacharet/microarray/GP3.html

* To whom correspondence should be addressed.
An estimate of large‐scale sequencing accuracy
Authors: Hill Fergal , Gemünd Christine , Benes Vladimir , Ansorge Wilhelm , Gibson Toby J
Published: July 2002

The accuracy of large‐scale DNA sequencing is difficult to estimate without redundant effort. We have found that the mobile genetic element IS10, a component of the transposon Tn10, has contaminated a significant number of clones in the public databases, as a result of the use of the transposon in bacterial cloning strain construction. These contaminations need to be annotated as such. More positively, by defining the range of sequence variation in IS10, we have been able to determine that the rate of sequencing errors is very low, most likely surpassing the stated aim of one error or less in ten thousand bases.