bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feature selection and transduction for
prediction of molecular bioactivity for drug design
Authors: Weston Jason , Pérez-Cruz Fernando , Bousquet Olivier , Chapelle Olivier , Elisseeff André , Schölkopf Bernhard 
Published: April 2003

Abstract
Motivation: In drug discovery a key task is to identify characteristics that separate active (binding) compounds from inactive (non-binding) ones. An automated prediction system can help reduce resources necessary to carry out this task.
Results: Two methods for prediction of molecular bioactivity for drug design are introduced and shown to perform well in a data set previously studied as part of the KDD (Knowledge Discovery and Data Mining) Cup 2001. The data is characterized by very few positive examples, a very large number of features (describing three-dimensional properties of the molecules) and rather different distributions between training and test data. Two techniques are introduced specifically to tackle these problems: a feature selection method for unbalanced data and a classifier which adapts to the distribution of the the unlabeled test data (a so-called transductive method). We show both techniques improve identification performance and in conjunction provide an improvement over using only one of the techniques. Our results suggest the importance of taking into account the characteristics in this data which may also be relevant in other problems of a similar type.
Availability: Matlab source code is available at http://www.kyb.tuebingen.mpg.de/bs/people/weston/kdd/kdd.html
Contact: jason.weston@tuebingen.mpg.de
Supplementary information: Supplementary material is available at http://www.kyb.tuebingen.mpg.de/bs/people/weston/kdd/kdd.html.
* To whom correspondence should be addressed.
Protein structure comparison by probability-based matching of secondary
structure elements
Authors: Shih Edward S.C. , Hwang Ming-Jing 
Published: April 2003

Abstract
Motivation: Protein structure comparison (PSC) has been used widely in studies of structural and functional genomics. However, PSC is computationally expensive and as a result almost all of the PSC methods currently in use look only for the optimal alignment and ignore many alternative alignments that are statistically significant and that may provide insight into protein evolution or folding.
Results: We have developed a new PSC method with efficiency to detect potentially viable alternative alignments in all-against-all database comparisons. The efficiency of the new PSC method derives from the ability to directly home in on a limited number of viable and ranked alignment solutions based on intuitively derived SSE (secondary structure element)-matching probabilities.
Availability: The new PSC tool is accessible at our lab website http://gln.ibms.sinica.edu.tw/software.php
Contact: mjhwang@ibms.sinica.edu.tw
Supplementary Information: Supplementary tables and figures for this paper can be found at the same website.
* To whom correspondence should be addressed.
RECSIM and INDSTATS: probabilities of identity in general genealogies
Authors: Dimitropoulou Polixeni , Cannings Chris 
Published: April 2003

Abstract
Summary: RECSIM takes a general genealogy and simulates the transmission of chromosomes through that genealogy. INDSTATS extracts some basic statistics from the output of RECSIM
Availability: The RECSIM and INDSTATS programs together with readme files READMESIM and READMESTATS can be downloaded from http://www.shef.ac.uk/mmge/chris/inbred.html
Contact: c.cannings@shef.ac.uk
* To whom correspondence should be addressed.
Genome-wide analysis of Bkm sequences (GATA repeats):
predominant association with sex chromosomes and potential role
in higher order chromatin organization and function
Authors: Subramanian Subbaya , Mishra Rakesh K. , Singh Lalji 
Published: April 2003

Abstract
Motivation: Bkm (Banded krait minor) satellite DNA sequences (GATA repeats) have been shown to be associated with the sex determining chromosomes of various eukaryotes and have been implicated in the evolution and differentiation of sex chromosomes in snakes. The objective of the study is to analyze the GATA repeats of human genome specifically, the Y-chromosome, and other model organisms to understand the possible function and potential role in higher order chromatin organization.
Results: Our extensive analysis of GATA repeats in the prokaryotic and eukaryotic genomes, which have been completely sequenced so far, has revealed that GATA repeats are absent in prokaryotes and have been gradually accumulated in higher organisms during the course of evolution. In human, the Y-chromosome has the highest GATA repeat density, which predominantly exists in the Yq centromeric region. Generally, occurrence of repeats in the genomes decreases steadily as the length of the repeat increases. In contrast, we report, that the occurrence of GATA repeats increases as the length of the repeat increases from six tandem repeats onwards and peaks at (GATA)10–12. This has not been observed with any other simple repeat. Distribution of (GATA)10–12 along the chromosome and their close proximity to Matrix Associated Regions (GATA-MAR) suggests that it may be demarking chromatin domains for a coordinated expression of genes residing in these domains. Supplementary data is available at http://www.ccmb.res.in/bkm/gata.htm.
Contact: lalji@ccmb.res.in
* To whom correspondence should be addressed.
Statistical tests for identifying differentially
expressed genes in time-course microarray experiments
Authors: Park Taesung , Yi Sung-Gon , Lee Seungmook , Lee Seung Yeoun , Yoo Dong-Hyun , Ahn Jun-Ik , Lee Yong-Sung 
Published: April 2003

Abstract
Motivation: Microarray technology allows the monitoring of expression levels for thousands of genes simultaneously. In time-course experiments in which gene expression is monitored over time, we are interested in testing gene expression profiles for different experimental groups. However, no sophisticated analytic methods have yet been proposed to handle time-course experiment data.
Results: We propose a statistical test procedure based on the ANOVA model to identify genes that have different gene expression profiles among experimental groups in time-course experiments. Especially, we propose a permutation test which does not require the normality assumption. For this test, we use residuals from the ANOVA model only with time-effects. Using this test, we detect genes that have different gene expression profiles among experimental groups. The proposed model is illustrated using cDNA microarrays of 3840 genes obtained in an experiment to search for changes in gene expression profiles during neuronal differentiation of cortical stem cells.
Availability: A set of programs written by R will be electronically sent upon request.
Contact: tspark@stats.snu.ac.kr
* To whom correspondence should be addressed.
Computer simulation of the cellular arrangement using physical
model in early cleavage of the nematode Caenorhabditis elegans
Authors: Kajita Atsushi , Yamamura Masayuki , Kohara Yuji 
Published: April 2003

Abstract
Motivation: The ultimate goal of bioinformatics is to reconstruct biological systems in the computer. Since biological systems have many levels, it is important to focus on an appropriate level. In our first application of computer modeling to the early development of the nematode Caenorhabditis elegans, we focus on the cellular arrangement in early embryos. This plays a very important role in cell fate determination by cell–cell interaction, and is regarded as a system, one level higher than the system of gene regulation within cells. It is largely restricted by physical conditions that seemed feasible to model by computer.
Results: We constructed a computer model of the C.elegans embryo, currently up to the 4-cell stage, using a deformable and dividable triangulated network. The model is based solely on cellular-level dynamics. We found that the optimal ranges of three parameters that affect the elongation of dividing cells led, in computer simulations, to almost the same cellular arrangements as in real embryos. The nature of the model and the relationship with real embryos are discussed.
Availability: The software is available upon request.
Contact: akajita@lab.nig.ac.jp
* To whom correspondence should be addressed.
Construction of reliable protein–protein interaction networks
with a new interaction generality measure
Authors: Saito Rintaro , Suzuki Harukazu , Hayashizaki Yoshihide 
Published: April 2003

Abstract
Motivation: Recent screening techniques have made large amounts of protein–protein interaction data available, from which biologically important information such as the function of uncharacterized proteins, the existence of novel protein complexes, and novel signal-transduction pathways can be discovered. However, experimental data on protein interactions contain many false positives, making these discoveries difficult. Therefore computational methods of assessing the reliability of each candidate protein–protein interaction are urgently needed.
Results: We developed a new ‘interaction generality’ measure (IG2) to assess the reliability of protein–protein interactions using only the topological properties of their interaction-network structure. Using yeast protein–protein interaction data, we showed that reliable protein–protein interactions had significantly lower IG2 values than less-reliable interactions, suggesting that IG2 values can be used to evaluate and filter interaction data to enable the construction of reliable protein–protein interaction networks.
Availability: The protein–protein interaction data used in this study along with the associated IG2 values are available at http://genome.gsc.riken.go.jp.
Contact: rgscerg@gsc.riken.go.jp
* To whom correspondence should be addressed.
† Present address: Institute for Advanced Biosciences, Keio University, 14-1 Baba-cho, Tsuruoka, Yamagata 997-0035, Japan.
Using multiple interdependency
to separate functional from phylogenetic correlations in protein alignments
Authors: Tillier Elisabeth R.M. , Lui Thomas W.H. 
Published: April 2003

Abstract
Motivation: Multiple sequence alignments of homologous proteins are useful for inferring their phylogenetic history and to reveal functionally important regions in the proteins. Functional constraints may lead to co-variation of two or more amino acids in the sequence, such that a substitution at one site is accompanied by compensatory substitutions at another site. It is not sufficient to find the statistical correlations between sites in the alignment because these may be the result of several undetermined causes. In particular, phylogenetic clustering will lead to many strong correlations.
Results: A procedure is developed to detect statistical correlations stemming from functional interaction by removing the strong phylogenetic signal that leads to the correlations of each site with many others in the sequence. Our method relies upon the accuracy of the alignment but it does not require any assumptions about the phylogeny or the substitution process. The effectiveness of the method was verified using computer simulations and then applied to predict functional interactions between amino acids in the Pfam database of alignments.
Availability: The program and supplementary figures tables are available from the site http://www.uhnres.utoronto.ca/tillier/depend2/dependency.html.
Contact: e.tillier@utoronto.ca
* To whom correspondence should be addressed.
Automated generation and refinement of protein signatures:
case study with G-protein coupled receptors
Authors: Sadowski Michael I. , Parish John Howard 
Published: April 2003

Abstract
Motivation: Previous work had established that it was possible to derive sparse signatures (essentially sequence-length motifs) by examining points of contact between residues in proteins of known three-dimensional (3D) structure. Many interesting protein families have very little tertiary structural information. Methods for deriving signatures using only primary and secondary-structural information were therefore developed.
Results: Two methods for deriving protein signatures using protein sequence information and predicted secondary structures are described. One method is based on a scoring approach, the other on the Genetic Algorithm (GA). The effectiveness of the method was tested on the superfamily of GPCRs and compared with the established hidden Markov model (HMM) method. The signature method is shown to perform well, detecting 68% of superfamily members before the first false positive sequence and detecting several distant relationships. The GA population was used to provide information on alignment regions of particular importance for selection of key residues.
Contact: howard@bmb.leeds.ac.uk
Supplementary information: Software developed for this project and further data are available online (http://bbsrc-bioinf.leeds.ac.uk/BIOINF/jhp/)
* To whom correspondence should be addressed.
GoFish finds genes with combinations of Gene Ontology attributes
Authors: Berriz Gabriel F. , White James V. , King Oliver D. , Roth Frederick P. 
Published: April 2003

Abstract
Summary: GoFish is a Java application that allows users to search for gene products with particular gene ontology (GO) attributes, or combinations of attributes. GoFish ranks gene products by the degree to which they satisfy a Boolean query. Four organisms are currently supported: Saccaromyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and M.musculus.
Availability: GoFish can be used freely through the www as a Java applet for Windows, Mac OS X, or Unix: http://llama.med.harvard.edu/Software.html.
Contact: fritz_roth@hms.harvard.edu
* To whom correspondence should be addressed.
EPPS: mining the COG database by an extended phylogenetic
patterns search
Authors: Reichard Klaus , Kaufmann Michael 
Published: April 2003

Abstract
Summary: EPPS runs under Microsoft Windows. It is an extended version of the phylogenetic patterns search (PPS). The output condition of PPS is the exact match of a user defined phylogenetic pattern with the pattern represented by the respective cluster of orthologous groups (COG). In contrast, the software described here is less restrictive. The user may define the accuracy of the search by the number of genomes that are allowed not to match the predefined phylogenetic pattern. Thus, EPPS has the advantage to detect COGs even if organisms defined to be included are not or organisms defined to be excluded are present in the output COGs.
Availability: EPPS is free and both windows executable and source code are available at http://www.uni-wh.de/de/nawi/institut/protein/epps.html
Contact: mika@uni-wh.de
* To whom correspondence should be addressed.
AFLPinSilico, simulating AFLP fingerprints
Authors: Rombauts Stephane , Van de Peer Yves , Rouzé Pierre 
Published: April 2003

Abstract
Summary: A drawback of the Amplified Fragment Length Polymorphism (AFLP) fingerprinting method is the difficulty to correlate the different fragments with their DNA sequence. The AFLPinSilico application presented here simulates AFLP experiments run on either cDNA or genomic sequences, producing virtual fingerprints that allow high throughput identification of AFLP fragments. The program also enables biologists to manage experiments through simulations done beforehand, thereby reducing the number of experiments that have to be run. AFLPinSilico is available through the www or as a stand-alone version, through a command line executable (available upon request, for any platform running PERL).
Availability: For academic use http://www.psb.rug.ac.be/bioinformatics/AFLPinSilico.html
Contact: strom@gengenp.rug.ac.be
* To whom correspondence should be addressed.
Symplastic Continuity between Companion Cells and the Translocation Stream: Long-Distance Transport Is Controlled by Retention and Retrieval Mechanisms in the Phloem
Authors: Ayre Brian G. , Keller Felix , Turgeon Robert 
Published: April 2003

Abstract
Substantial symplastic continuity appears to exist between companion cells (CCs) and sieve elements of the phloem, which suggests that small solutes within the CC are subject to indiscriminate long-distance transport via the translocation stream. To test this hypothesis, the distributions of exotic and endogenous solutes synthesized in the CCs of minor veins were studied. Octopine, a charged molecule derived from arginine and pyruvate, was efficiently transported through the phloem but was also transferred in substantial amounts to the apoplast, and presumably other non-phloem compartments. The disaccharide galactinol also accumulated in non-phloem compartments, but long-distance transport was limited. Conversely, sucrose, raffinose, and especially stachyose demonstrated reduced accumulation and efficient transport out of the leaf. We conclude that small metabolites in the cytosol of CCs do enter the translocation stream indiscriminately but are also subject to distributive forces, such as nonselective and carrier-mediated membrane transport and symplastic dispersal, that may effectively clear a compound from the phloem or retain it for long-distance transport. A model is proposed in which the transport of oligosaccharides is an adaptive strategy to improve photoassimilate retention, and consequently translocation efficiency, in the phloem.
Natural Abundance Carbon Isotope Composition of Isoprene Reflects Incomplete Coupling between Isoprene Synthesis and Photosynthetic Carbon Flow
Authors: Affek Hagit P. , Yakir Dan 
Published: April 2003

Abstract
Isoprene emission from leaves is dynamically coupled to photosynthesis through the use of primary and recent photosynthate in the chloroplast. However, natural abundance carbon isotope composition (δ13C) measurements in myrtle (Myrtus communis), buckthorn (Rhamnus alaternus), and velvet bean (Mucuna pruriens) showed that only 72% to 91% of the variations in the δ13C values of fixed carbon were reflected in the δ13C values of concurrently emitted isoprene. The results indicated that 9% to 28% carbon was contributed from alternative, slow turnover, carbon source(s). This contribution increased when photosynthesis was inhibited by CO2-free air. The observed variations in the δ13C of isoprene under ambient and CO2-free air were consistent with contributions to isoprene synthesis in the chloroplast from pyruvate associated with cytosolic Glc metabolism. Irrespective of alternative carbon source(s), isoprene was depleted in 13C relative to mean photosynthetically fixed carbon by 4‰ to 11‰. Variable13C discrimination, its increase by partially inhibiting isoprene synthesis with fosmidomicin, and the associated accumulation of pyruvate suggested that the main isotopic discrimination step was the deoxyxylulose-5-phosphate synthase reaction.
Vulnerability of Xylem Vessels to Cavitation in Sugar Maple. Scaling from Individual Vessels to Whole Branches
Authors: Melcher Peter J. , Zwieniecki Maciej A. , Holbrook N. Michele 
Published: April 2003

Abstract
The relation between xylem vessel age and vulnerability to cavitation of sugar maple (Acer saccharum Marsh.) was quantified by measuring the pressure required to force air across bordered pit membranes separating individual xylem vessels. We found that the bordered pit membranes of vessels located in current year xylem could withstand greater applied gas pressures (3.8 MPa) compared with bordered pit membranes in vessels located in older annular rings (2.0 MPa). A longitudinal transect along 6-year-old branches indicated that the pressure required to push gas across bordered pit membranes of current year xylem did not vary with distance from the growing tip. To understand the contribution of age-related changes in vulnerability to the overall resistance to cavitation, we combined data on the pressure thresholds of individual xylem vessels with measurements of the relative flow rate through each annual ring. The annual ring of the current year contributed only 16% of the total flow measured on 10-cm-long segments cut from 6-year-old branches, but it contributed more than 70% of the total flow when measured through 6-year-old branches to the point of leaf attachment. The vulnerability curve calculated using relative flow rates measured on branch segments were similar to vulnerability curves measured on 6-year-old branches (pressure that reduces hydraulic conductance by 50% = 1.6–2.4 MPa), whereas the vulnerability curve calculated using relative flow rates measured on 6-year-old branches were similar to ones measured on the extension growth of the current year (pressure that reduces hydraulic conductance by 50% = 3.8 MPa). These data suggest that, in sugar maple, the xylem of the current year can withstand larger xylem tensions than older wood and dominates water delivery to leaves.
Freezing Sensitivity in the sfr4 Mutant of Arabidopsis Is Due to Low Sugar Content and Is Manifested by Loss of Osmotic Responsiveness
Authors: Uemura Matsuo , Warren Gareth , Steponkus Peter L. 
Published: April 2003

Abstract
Protoplasts were tested to determine whether the freezing sensitivity of the sfr4 (sensitive to freezing) mutant of Arabidopsis was due to the mutant's deficiency in soluble sugars after cold acclimation. When grown under nonacclimated conditions,sfr4 protoplasts possessed freezing tolerance similar to that of wild type, with the temperature at which 50% of protoplasts are injured (LT50) of −4.5°C. In both wild-type andsfr4 protoplasts, expansion-induced lysis was the predominant lesion between −2°C and −4°C, but its incidence was low (approximately 10%); below −5°C, loss of osmotic responsiveness (LOR) was the predominant lesion. After cold acclimation, the LT50 was decreased to only −5.6°C forsfr4 protoplasts, compared with −9.1°C for wild-type protoplasts. Although expansion-induced lysis was precluded in both types of protoplasts, the sfr4 protoplasts remained susceptible to LOR. After incubation of seedlings in Suc solution in the dark at 2°C, freezing tolerance and the incidence of freeze-induced lesions in sfr4 protoplasts were examined. The freezing tolerance of isolated protoplasts (LT50 of −9°C) and the incidence of LOR were now similar for wild type and sfr4. These results indicate that the freezing sensitivity of cold-acclimated sfr4 is due to its continued susceptibility to LOR (associated with lyotropic formation of the hexagonal II phase) and associated with the low sugar content of its cells.
Disruption of Apyrases Inhibits Pollen Germination in Arabidopsis
Authors: Steinebrunner Iris , Wu Jian , Sun Yu , Corbett Ashley , Roux Stanley J. 
Published: April 2003

Abstract
In Arabidopsis, we previously identified two highly similar apyrases, AtAPY1 and AtAPY2. Here, T-DNA knockout (KO) mutations of each gene were isolated in a reverse genetic approach. The single KO mutants lacked a discernible phenotype. The double KO mutants, however, exhibited a complete inhibition of pollen germination, and this correlated with positive β-glucuronidase staining in the pollen of apyrase promoter:β-glucuronidase fusion transgenic lines. The vast majority of the pollen grains of these mutants were identical to wild type in size, shape, and nuclear state and were viable as assayed by metabolic activity and plasma membrane integrity. Complementation with either AtAPY1 or AtAPY2 cDNA rescued pollen germination, confirming that the phenotype was apyrase specific. Despite the redundancy of the two apyrases in rescue potential, transmission analyses suggested a greater role for AtAPY2 in male gamete success. The effect of mutant apyrase on the transmission through the female gametophyte was only marginal, and embryo development appeared normal in the absence of apyrases. The male-specific double KO mutation is fully penetrant and shows that apyrases play a crucial role in pollen germination.