bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assigning transmembrane segments to helices in intermediate-resolution structures
Authors: Enosh Angela , Fleishman Sarel J. , Ben-Tal Nir , Halperin Dan 
Published: July 2004

Abstract
Motivation: Transmembrane (TM) proteins that form α-helix bundles constitute approximately 50% of contemporary drug targets. Yet, it is difficult to determine their high-resolution (&lt; 4 Å) structures. Some TM proteins yield more easily to structure determination using cryo electron microscopy (cryo-EM), though this technique most often results in lower resolution structures, precluding an unambiguous assignment of TM amino acid sequences to the helices seen in the structure. We present computational tools for assigning the TM segments in the protein's sequence to the helices seen in cryo-EM structures.
Results: The method examines all feasible TM helix assignments and ranks each one based on a score function that was derived from loops in the structures of soluble α-helix bundles. A set of the most likely assignments is then suggested. We tested the method on eight TM chains of known structures, such as bacteriorhodopsin and the lactose permease. Our results indicate that many assignments can be rejected at the outset, since they involve the connection of pairs of remotely placed TM helices. The correct assignment received a high score, and was ranked highly among the remaining assignments. For example, in the lactose permease, which contains 12 TM helices, most of which are connected by short loops, only 12 out of 479 million assignments were found to be feasible, and the native one was ranked first.
Availability: The program and the non-redundant set of protein structures used here are available at http://www.cs.tau.ac.il/~angela
TraitMap: an XML-based genetic-map database combining multigenic loci and biomolecular networks
Authors: Heida Naohiko , Hasegawa Yoshikazu , Mochizuki Yoshiki , Hirosawa Katsura , Konagaya Akihiko , Toyoda Tetsuro 
Published: July 2004

Abstract
Motivation: Most ordinary traits are well described by multiple measurable parameters. Thus, in the course of elucidating the genes responsible for a given trait, it is necessary to conduct and integrate the genetic mapping of each parameter. However, the integration of multiple mapping results from different publications is prevented by the fact that they are conventionally published and accumulated in printed forms or graphics which are difficult for computers to reuse for further analyses.
Results: We have defined an XML-based schema as a container of genetic mapping results, and created a database named TraitMap containing curator-checked data records based on published papers of mapping results in Homosapiens, Mus musculus, and Arabidopsis thaliana. TraitMap is the first database of mapping charts in genetics, and is integrated in a web-based retrieval framework: termed Genome ⇔ Phenome Superhighway (GPS) system, where it is possible to combine and visualize multiple mapping records in a two-dimensional display. Since most traits are regulated by multiple genes, the system associates every combination of genetic loci to biomolecular networks, and thus helps us to estimate molecular-level candidate networks responsible for a given trait. It is demonstrated that a combined analysis of two diabetes-related traits (susceptibility to insulin resistance and non-HDL cholesterol level) suggests that molecular-level relationships such as the interaction among leptin receptor (Lepr), peroxisome proliferators-activated receptor-gamma (Pparg) and insulin receptor substrate 1 (Irs1), are candidate causal networks affecting the traits in a multigenic manner.
Availability: TraitMap database and GPS are accessible at http://omicspace.riken.jp/gps/
Supplementary information: See http://omicspace.riken.jp/info/traitmap.html
Inferring quantitative models of regulatory networks from expression data
Authors: Nachman I. , Regev A. , Friedman N. 
Published: July 2004

Abstract
Motivation: Genetic networks regulate key processes in living cells. Various methods have been suggested to reconstruct network architecture from gene expression data. However, most approaches are based on qualitative models that provide only rough approximations of the underlying events, and lack the quantitative aspects that are critical for understanding the proper function of biomolecular systems.
Results: We present fine-grained dynamical models of gene transcription and develop methods for reconstructing them from gene expression data within the framework of a generative probabilistic model. Unlike previous works, we employ quantitative transcription rates, and simultaneously estimate both the kinetic parameters that govern these rates, and the activity levels of unobserved regulators that control them. We apply our approach to expression datasets from yeast and show that we can learn the unknown regulator activity profiles, as well as the binding affinity parameters. We also introduce a novel structure learning algorithm, and demonstrate its power to accurately reconstruct the regulatory network from those datasets.
Improved techniques for the identification of pseudogenes
Authors: Coin L. , Durbin R. 
Published: July 2004

Abstract
Motivation: Pseudogenes are the remnants of genomic sequences of genes which are no longer functional. They are frequent in most eukaryotic genomes, and an important resource for comparative genomics. However, pseudogenes are often mis-annotated as functional genes in sequence databases. Current methods for identifying pseudogenes include methods which rely on the presence of stop codons and frameshifts, as well as methods based on the ratio of non-silent to silent nucleotide substitution rates (dN/dS). A recent survey concluded that 50% of human pseudogenes have no detectable truncation in their pseudo-coding regions, indicating that the former methods lack sensitivity. The latter methods have been used to find sets of genes enriched for pseudogenes, but are not specific enough to accurately separate pseudogenes from expressed genes.
Results: We introduce a program called pseudogene inference from loss of constraint (PSILC) which incorporates novel methods for separating pseudogenes from functional genes. The methods calculate the log-odds score that evolution along the final branch of the gene tree to the query gene has been according to the following constraints: A neutral nucleotide model compared to a Pfam domain encoding model (PSILCnuc/dom);A protein coding model compared to a Pfam domain encoding model (PSILCprot/dom). Using the manual annotation of human chromosome 6, we show that both these methods result in a more accurate classification of pseudogenes than dN/dS when a Pfam domain alignment is available.
Availability: PSILC is available from http://www.sanger.ac.uk/Software/PSILC
Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens
Authors: Srinivasan K.N. , Zhang G.L. , Khan A.M. , August J.T. , Brusic V. 
Published: July 2004

Abstract
Motivation: Processing and presentation of major histocompatibility complex class I antigens to cytotoxic T-lymphocytes is crucial for immune surveillance against intracellular bacteria, parasites, viruses and tumors. Identification of antigenic regions on pathogen proteins will play a pivotal role in designer vaccine immunotherapy. We have developed a system that not only identifies high binding T-cell antigenic epitopes, but also class I T-cell antigenic clusters termed immunological hot spots.
Methods: MULTIPRED, a computational system for promiscuous prediction of HLA class I binders, uses artificial neural networks (ANN) and hidden Markov models (HMM) as predictive engines. The models were rigorously trained, tested and validated using experimentally identified HLA class I T-cell epitopes from human melanoma related proteins and human papillomavirus proteins E6 and E7. We have developed a scoring scheme for identification of immunological hot spots for HLA class I molecules, which is the sum of the highest four predictions within a window of 30 amino acids.
Results: Our predictions against experimental data from four melanoma-related proteins showed that MULTIPRED ANN and HMM models could predict T-cell epitopes with high accuracy. The analysis of proteins E6 and E7 showed that ANN models appear to be more accurate for prediction of HLA-A3 hot spots and HMM models for HLA-A2 predictions. For illustration of its utility we applied MULTIPRED for prediction of promiscuous T-cell epitopes in all four SARS coronavirus structural proteins. MULTIPRED predicted HLA-A2 and HLA-A3 hot spots in each of these proteins.
Exploring Williams–Beuren syndrome using myGrid
Authors: Stevens R. D. , Tipney H. J. , Wroe C. J. , Oinn T. M. , Senger M. , Lord P. W. , Goble C. A. , Brass A. , Tassabehji M. 
Published: July 2004

Abstract
Motivation: In silico experiments necessitate the virtual organization of people, data, tools and machines. The scientific process also necessitates an awareness of the experience base, both of personal data as well as the wider context of work. The management of all these data and the co-ordination of resources to manage such virtual organizations and the data surrounding them needs significant computational infra-structure support.
Results: In this paper, we show that myGrid, middleware for the Semantic Grid, enables biologists to perform and manage in silico experiments, then explore and exploit the results of their experiments. We demonstrate myGrid in the context of a series of bioinformatics experiments focused on a 1.5 Mb region on chromosome 7 which is deleted in Williams–Beuren syndrome (WBS). Due to the highly repetitive nature of sequence flanking/in the WBS critical region (WBSCR), sequencing of the region is incomplete leaving documented gaps in the released sequence. myGrid was used in a series of experiments to find newly sequenced human genomic DNA clones that extended into these ‘gap’ regions in order to produce a complete and accurate map of the WBSCR. Once placed in this region, these DNA sequences were analysed with a battery of prediction tools in order to locate putative genes and regulatory elements possibly implicated in the disorder. Finally, any genes discovered were submitted to a range of standard bioinformatics tools for their characterization. We report how myGrid has been used to create workflows for these in silico experiments, run those workflows regularly and notify the biologist when new DNA and genes are discovered. The myGrid services collect and co-ordinate data inputs and outputs for the experiment, as well as much provenance information about the performance of experiments on WBS.
Availability: The myGrid software is available via http://www.mygrid.org.uk
IMGT/JunctionAnalysis: the first tool for the analysis of the immunoglobulin and T cell receptor complex V–J and V–D–J JUNCTIONs
Authors: Monod Mehdi Yousfi , Giudicelli Véronique , Chaume Denys , Lefranc Marie-Paule 
Published: July 2004

Abstract
Motivation: To create the enormous diversity of 1012 immunoglobulins (IG) and T cell receptors (TR) per individual, very complex mechanisms occur at the DNA level: the combinatorial diversity results from the junction of the variable (V), diversity (D) and joining (J) genes; the N-diversity represents the addition at random of nucleotides not encoded in the genome; and somatic hypermutations occur in IG rearranged sequences. The accurate annotation of the junction between V, D, J genes in rearranged IG and TR sequences represents therefore a huge challenge by its uniqueness and complexity. We developed IMGT/JunctionAnalysis to analyse automatically in detail the IG and TR junctions, according to the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts.
Results: IMGT/JunctionAnalysis is the first tool for the detailed analysis of the IG and TR complex V–J and V–D–J JUNCTION(s). It delimits, at the nucleotide level, the genes resulting from the combinatorial diversity. It identifies accurately the D genes in the junctions of IG heavy (IGH), TR beta (TRB) and delta (TRD) chains. It delimits the palindromic P-REGION(s) and the N-REGION(s) resulting from the N-diversity. It evaluates the number of somatic hypermutations for each gene, within the JUNCTION. IMGT/JunctionAnalysis is capable of analysing, in a single run, an unlimited number of junctions from the same species (currently human or mouse) and from the same locus.
Availability: IMGT/JunctionAnalysis is available from the IMGT Home page at http://imgt.cines.fr
Into the heart of darkness: large-scale clustering of human non-coding DNA
Authors: Bejerano Gill , Haussler David , Blanchette Mathieu 
Published: July 2004

Abstract
Motivation: It is currently believed that the human genome contains about twice as much non-coding functional regions as it does protein-coding genes, yet our understanding of these regions is very limited.
Results: We examine the intersection between syntenically conserved sequences in the human, mouse and rat genomes, and sequence similarities within the human genome itself, in search of families of non-protein-coding elements. For this purpose we develop a graph theoretic clustering algorithm, akin to the highly successful methods used in elucidating protein sequence family relationships.
The algorithm is applied to a highly filtered set of about 700 000 human–rodent evolutionarily conserved regions, not resembling any known coding sequence, which encompasses 3.7% of the human genome. From these, we obtain roughly 12 000 non-singleton clusters, dense in significant sequence similarities. Further analysis of genomic location, evidence of transcription and RNA secondary structure reveals many clusters to be significantly homogeneous in one or more characteristics. This subset of the highly conserved non-protein-coding elements in the human genome thus contains rich family-like structures, which merit in-depth analysis.
Availability: Supplementary material to this work is available at http://www.soe.ucsc.edu/~jill/dark.html
Automatic Quality Assessment of Peptide Tandem Mass Spectra
Authors: Bern Marshall , Goldberg David , McDonald W. Hayes , Yates John R. 
Published: July 2004

Abstract
Motivation: A powerful proteomics methodology couples high-performance liquid chromatography (HPLC) with tandem mass spectrometry and database-search software, such as SEQUEST. Such a set-up, however, produces a large number of spectra, many of which are of too poor quality to be useful. Hence a filter that eliminates poor spectra before the database search can significantly improve throughput and robustness. Moreover, spectra judged to be of high quality, but that cannot be identified by database search, are prime candidates for still more computationally intensive methods, such as de novo sequencing or wider database searches including post-translational modifications.
Results: We report on two different approaches to assessing spectral quality prior to identification: binary classification, which predicts whether or not SEQUEST will be able to make an identification, and statistical regression, which predicts a more universal quality metric involving the number of b- and y-ion peaks. The best of our binary classifiers can eliminate over 75% of the unidentifiable spectra while losing only 10% of the identifiable spectra. Statistical regression can pick out spectra of modified peptides that can be identified by a de novo program but not by SEQUEST. In a section of independent interest, we discuss intensity normalization of mass spectra.
SCOPEC: a database of protein catalytic domains
Authors: George Richard A. , Spriggs Ruth V. , Thornton Janet M. , Al-Lazikani Bissan , Swindells Mark B. 
Published: July 2004

Abstract
Motivation: Domains are the units of protein structure, function and evolution. It is therefore essential to utilize knowledge of domains when studying the evolution of function, or when assigning function to genome sequence data. For this purpose, we have developed a database of catalytic domains, SCOPEC, by combining structural domain information from SCOP, full-length sequence information from Swiss-Prot, and verified functional information from the Enzyme Classification (EC) database. Two major problems need to be overcome to create a database of domain–function relationships; (1) for sequences, EC numbers are typically assigned to whole sequences rather than the functional unit, and (2) The Protein Data Bank (PDB) structures elucidated from a larger multi-domain protein will often have EC annotation although the relevant catalytic domain may lie elsewhere.
Results: SCOPEC entries have high quality enzyme assignments; having passed both computational and manual checks. SCOPEC currently contains entries for 75% of all EC annotations in the PDB. Overall, EC number is fairly well conserved within a superfamily, even when the proteins are distantly related. Initial analysis is encouraging; suggesting that there is a 50:50 chance of conserved function in distant homologues first detected by a third iteration PSI-BLAST search. Therefore, we envisage that a knowledge-based approach to function assignment using the domain–EC relationships in SCOPEC will gain a marked improvement over this base line.
Availability: The SCOPEC database is a valuable resource in the analysis and prediction of protein structure and function. It can be obtained or queried at our website http://www.enzome.com
Selecting biomedical data sources according to user preferences
Authors: Boulakia Sarah Cohen , Lair Séverine , Stransky Nicolas , Graziani Stéphane , Radvanyi François , Barillot Emmanuel , Froidevaux Christine 
Published: July 2004

Abstract
Motivation: Biologists are now faced with the problem of integrating information from multiple heterogeneous public sources with their own experimental data contained in individual sources. The selection of the sources to be considered is thus critically important.
Results: Our aim is to support biologists by developing a module based on an algorithm that presents a selection of sources relevant to their query and matched to their own preferences. We approached this task by investigating the characteristics of biomedical data and introducing several preference criteria useful for bioinformaticians. This work was carried out in the framework of a project which aims to develop an integrative platform for the multiple parametric analysis of cancer. We illustrate our study through an elementary biomedical query occurring in a CGH analysis scenario.
Availability: http://www.lri.fr/~cohen/dss/dss.html
Amino and cyano N atoms in competitive situations: which is the best hydrogen-bond acceptor? A crystallographic database investigation
Authors: Ziao Nahossé , Graton Jérôme , Laurence Christian , Le Questel Jean-Yves 
Published: July 2004

The relative hydrogen-bond acceptor abilities of amino and cyano N atoms have been investigated using data retrieved from the Cambridge Structural Database and via ab initio molecular orbital calculations. Surveys of the CSD for hydrogen bonds between HX (X = N, O) donors, N—T—C≡N (push–pull nitriles) and N—(Csp
3)
n
—C≡N molecular fragments show that the hydrogen bonds are more abundant on the nitrile than on the amino nitrogen. In the push–pull family, in which T is a transmitter of resonance effects, the hydrogen-bonding ability of the cyano nitrogen is increased by conjugative interactions between the lone pair of the amino substituent and the C≡N group: a clear example of resonance-assisted hydrogen bonding. The strength of the hydrogen-bonds on the cyano nitrogen in this family follows the experimental order of hydrogen-bond basicity, as observed in solution through the pK
HB scale. The number of hydrogen bonds established on the amino nitrogen is greater for aliphatic aminonitriles N—(Csp
3)
n
—C≡N, but remains low. This behaviour reflects the greater sensitivity of the amino nitrogen to steric hindrance and the electron-withdrawing inductive effect compared with the cyano nitrogen. Ab initio molecular orbital calculations (B3LYP/6-31+G** level) of electrostatic potentials on the molecular surface around each nitrogen confirm the experimental observations.
The LNLS soft X-ray spectroscopy beamline
Authors: Tolentino H. , Compagnon-Cailhol V. , Vicentin F. C. , Abbate M. 
Published: July 2004

The soft X-ray spectroscopy beamline installed at a bending-magnet source at the LNLS is described. The optics are designed to cover energies from 800 to 4000 eV with good efficiency. The focusing element is a gold-coated toroidal mirror with an angle of incidence of 17 mrad. The UHV double-crystal monochromator has three pairs of crystals, Si (111), InSb (111) and beryl (101¯0), that can be selected by a sliding movement. The UHV workstation is equipped with an ion gun, an electron gun, an electron analyser, LEED optics, an open channeltron and a photodiode array. This beamline is intended for photoemission, photoabsorption, reflectivity and dichroism experiments.
Design of a high-flux and high-resolution VUV bending-magnet beamline
Authors: Hsieh T.-F. , Huang L.-R. , Chung S.-C. , Dann T.-E. , Tseng P.-C. , Chen C. T. , Tsang K.-L. 
Published: July 2004

A high-flux and high-resolution VUV beamline (4–40 eV) has been designed and is under construction at SRRC. This beamline, which collects 50 mrad of horizontal radiation, uses a 6 m cylindrical-grating monochromator with an incident angle of 70° instead of the conventional normal-incidence-monochromator (NIM) design. Special features, such as movable entrance slit, bendable vertical focusing mirror and movable curved exit slit, are employed to enhance greatly the beamline performance. With both slit openings set at 10 µm, the energy-resolving power can reach as high as 70000. Photon fluxes of 1 × 1013 and 1 × 1010 photons s−1 are calculated for energy-resolving powers of 1000 and 40000, respectively. The best image size at the sample position is smaller than 0.45 × 0.2 mm.
Layered structure analysis of GMR multilayers by X-ray reflectometry using the anomalous dispersion effect
Authors: Hirano Tatsumi , Usami Katsuhisa , Ueda Kazuhiro , Hoshiya Hiroyuki 
Published: July 2004

As a basic layered structure for giant magnetoresistive (GMR) heads, NiFe/Cu/NiFe/Ta/Si substrate was measured by X-ray reflectometry at Cu Kα, Cu Kβ and Cu K-absorption-edge energies. The accuracy of both the Cu thickness and the interface width between the upper NiFe and the Cu layers was found to improve in the order Cu Kα < Cu Kβ < Cu K-edge. The final thickness and interface width values obtained from Cu Kβ reflectivity are in good agreement with those from the Cu K-edge. The anomalous-dispersion effect is useful in the more accurate analysis of the layered structure of transition metal multilayers because it causes a large difference in the refractive indices of specific elements near the absorption edge. The Kβ X-rays, which can be produced from conventional X-ray sources, are also available for the accurate analysis of reflectivity measurements.
Micro X-ray diffraction analysis of thin films using grazing-exit conditions
Authors: Noma Takashi , Iida Atsuo 
Published: July 2004

An X-ray diffraction technique using a hard X-ray microbeam for thin-film analysis has been developed. To optimize the spatial resolution and the surface sensitivity, the X-ray microbeam strikes the sample surface at a large glancing angle while the diffracted X-ray signal is detected with a small (grazing) exit angle. Kirkpatrick–Baez optics developed at the Photon Factory were used, in combination with a multilayer monochromator, for focusing X-rays. The focused beam size was about 10 × 10 µm. X-ray diffraction patterns of Pd, Pt and their layered structure were measured. Using a small exit angle, the signal-to-background ratio was improved due to a shallow escape depth. Under the grazing-exit condition, the refraction effect of diffracted X-rays was observed, indicating the possibility of surface sensitivity.