3D-Garden: a system for modelling protein-protein complexes based on conformational refinement of ensembles generated with the marching cubes algorithm

Motivation: Reliable structural modelling of protein–proteincomplexes has widespread application, from drug design to advancingour knowledge of protein interactions and function. This workaddresses three important issues in protein–protein docking:implementing backbone flexibility, incorporating prior indicationsfrom experiment and bioinformatics, and providing public accessvia a server. 3D-Garden (Global And Restrained Docking ExplorationNexus), our benchmarked and server-ready flexible docking system,allows sophisticated programming of surface patches by the uservia a facet representation of the interactors’ molecularsurfaces (generated with the marching cubes algorithm). Flexibilityis implemented as a weighted exhaustive conformer search foreach clashing pair of molecular branches in a set of 5000 modelsfiltered from around 340 000 initially. Results: In a non-global assessment, carried out strictly accordingto the protocols for number of models considered and model qualityof the Critical Assessment of Protein Interactions (CAPRI) experiment,over the widely-used Benchmark 2.0 of 84 complexes, 3D-Gardenidentifies a set of ten models containing an acceptable or bettermodel in 29/45 test cases, including one with large conformationalchange. In 19/45 cases an acceptable or better model is rankedfirst or second out of 340 000 candidates. Availability: http://www.sbg.bio.ic.ac.uk/3dgarden (server) Contact: v.lesk{at}ic.ac.uk Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Burkhard Rost     

Gut evacuation rates and ingestion rates of Eudiaptomus graciloides measured by means of the gut fluorescence method

Journal of Plankton Research, 8, 973–983, 1986 FIg. 2. Time-dependent changes in the gut content (percentageof initial ng pigment) of E. gro.ciloides at different temperaturesunder simultaneous feeding. Fig. 4. The relationship between instantaneous evacuation rateand temperature of E. graciloides. The regresston equation forfeeding animals: y = 0.0044 e(0.141 ) (r² = 0.90). For comparisonthe results of non-feeding animals are indicated with open circles.     

Influence of the 3'-UTR-length of mKIAA cDNAs and their Sequence Features to the mRNA Expression Level in the Brain

We have previously described the sequence features of 1500 mouseKIAA (mKIAA) genes in comparison with those of human KIAA genes(Okazaki, N., Kikuno, R., Inamoto, S., Hara, Y., Nagase, T.,Ohara, O., and Koga, H. 2002, DNA Res., 9, 179–188; Okazaki,N., Kikuno, R., Ohara, R., Inamoto, S., Aizawa, H., Yuasa, S.,Nakajima, D., Nagase, T., Ohara, O., and Koga, H. 2003, DNARes., 10, 35–48; Okazaki, N., Kikuno, R., Ohara, R., Inamoto,S., Koseki, H., Hiraoka, S., Saga, Y., Nagase, T., Ohara, O.,and Koga, H. 2003, DNA Res., 10, 167–180; and Okazaki,N., F-Kikuno, R., Ohara, R., Inamoto, S., Koseki, H., Hiraoka,S., Saga, Y., Seino, S., Nishimura, M., Kaisho, T., Hoshino,K., Kitamura, H., Nagase, T., Ohara, O., and Koga, H. 2004,DNA Res., 11, 205–218). To validate the orthologous relationshipbetween mKIAA and KIAA genes in detail, we examined their chromosomalpositions and evolutionary rate of synonymous substitutionsand confirmed that >93% of the mKIAA/KIAA gene pairs areorthologous. During the sequence analysis of mKIAA genes, wefound that 3'-untranslated region (3'-UTR) lengths of mKIAAand KIAA genes are extremely long. In the meanwhile, we havealso examined the tissue-specific expression of 1700 mKIAA genesusing cDNA microarray and verified predominantly their expressionin adult brain (Koga, H., Yuasa, S., Nagase, T., Shimada, K.,Nagano, M., Imai, K., Ohara, R., Nakajima, D., Murakami, M.,Kawai, M., Miki, F., Magae, J., Inamoto, S., Okazaki, N., Ohara,O. 2004, DNA Res., 11, 293–304). To connect these twoevidences, we statistically analysed the relationship betweenthem by using the mKIAA genes. Consequently, a positive correlationwas observed between the 3'-UTR lengths and the relative expressionintensities in adult brain. Furthermore, we searched sequenceelements in the 3'-UTR possibly related with their expressionand found some candidates regarding the brain-specific expression.     

Robust accurate identification of peptides (RAId): deciphering MS2 data using a structured library search with de novo based statistics

Motivation: The key to MS -based proteomics is peptide sequencing.The major challenge in peptide sequencing, whether library searchor de novo, is to better infer statistical significance andbetter attain noise reduction. Since the noise in a spectrumdepends on experimental conditions, the instrument used andmany other factors, it cannot be predicted even if the peptidesequence is known. The characteristics of the noise can onlybe uncovered once a spectrum is given. We wish to overcome suchissues. Results: We designed RAId to identify peptides from their associatedtandem mass spectrometry data. RAId performs a novel de novosequencing followed by a search in a peptide library that wecreated. Through de novo sequencing, we establish the spectrum-specificbackground score statistics for the library search. When thedatabase search fails to return significant hits, the top-rankingde novo sequences become potential candidates for new peptidesthat are not yet in the database. The use of spectrum-specificbackground statistics seems to enable RAId to perform well evenwhen the spectral quality is marginal. Other important featuresof RAId include its potential in de novo sequencing alone andthe ease of incorporating post-translational modifications. Availability: Programs implementing the methods described areavailable from the authors on request. Contact: yyu{at}ncbi.nlm.nih.gov Supplementary information: ftp://ftp.ncbi.nih.gov/pub/yyu/Proteomics/MSMS/RAId/MSMS_bioinfo_supp.pdf     

Model-based deconvolution of genome-wide DNA binding

Motivation: Chromatin immunoprecipitation followed by hybridizationto a genomic tiling microarray (ChIP-chip) is a routinely usedprotocol for localizing the genomic targets of DNA-binding proteins.The resolution to which binding sites in this assay can be identifiedis commonly considered to be limited by two factors: (1) theresolution at which the genomic targets are tiled in the microarrayand (2) the large and variable lengths of the immunoprecipitatedDNA fragments. Results: We have developed a generative model of binding sitesin ChIP-chip data and an approach, MeDiChI, for efficientlyand robustly learning that model from diverse data sets. Wehave evaluated MeDiChI's performance using simulated data, aswell as on several diverse ChIP-chip data sets collected onwidely different tiling array platforms for two different organisms(Saccharomyces cerevisiae and Halobacterium salinarium NRC-1).We find that MeDiChI accurately predicts binding locations toa resolution greater than that of the probe spacing, even foroverlapping peaks, and can increase the effective resolutionof tiling array data by a factor of 5x or better. Moreover,the method's performance on simulated data provides insightsinto effectively optimizing the experimental design for increasedbinding site localization accuracy and efficacy. Availability: MeDiChI is available as an open-source R package,including all data, from http://baliga.systemsbiology.net/medichi. Contact: dreiss{at}systemsbiology.org Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

Unequal group variances in microarray data analyses

Motivation: In searching for differentially expressed (DE) genesin microarray data, we often observe a fraction of the genesto have unequal variability between groups. This is not an issuein large samples, where a valid test exists that uses individualvariances separately. The problem arises in the small-samplesetting, where the approximately valid Welch test lacks sensitivity,while the more sensitive moderated t-test assumes equal variance. Methods: We introduce a moderated Welch test (MWT) that allowsunequal variance between groups. It is based on (i) weightingof pooled and unpooled standard errors and (ii) improved estimationof the gene-level variance that exploits the information fromacross the genes. Results: When a non-trivial proportion of genes has unequalvariability, false discovery rate (FDR) estimates based on thestandard t and moderated t-tests are often too optimistic, whilethe standard Welch test has low sensitivity. The MWT is shownto (i) perform better than the standard t, the standard Welchand the moderated t-tests when the variances are unequal betweengroups and (ii) perform similarly to the moderated t, and betterthan the standard t and Welch tests when the group variancesare equal. These results mean that MWT is more reliable thanother existing tests over wider range of data conditions. Availability: R package to perform MWT is available at http://www.meb.ki.se/~yudpaw Contact: yudi.pawitan{at}ki.se Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

PETALIFERA HABEI, A NEW SPECIES FROM JAPAN ADDENDUM

Since Petalifera habei was described in the Proceedings, 34,1, 12–18, April 1960, I have received from Dr. K. Babaa short account of the same species in Publ. Seto. mar. biol.Lab. 7, 3, 337–338. December, 1959, under the title "Thegenus Petalifera and a new species, P. ramosa, from Japan".I was unaware that Dr. Baba intended to describe it. As hispaper antedates mine, his name, Petalifera ramosa, must replaceP. Habei.     

A new algorithm for cluster analysis of genomic methylation: the Helicobacter pylori case

Motivation: The genomic methylation analysis is useful to typebacteria that have a high number of expressed type II methyltransferases.Methyltransferases are usually committed to Restriction andModification (R-M) systems, in which the restriction endonucleaseimposes high pressure on the expression of the cognate methyltransferasethat hinder R-M system loss. Conventional cluster methods donot reflect this tendency. An algorithm was developed for dendrogramconstruction reflecting the propensity for conservation of R-MType II systems. Results: The new algorithm was applied to 52 Helicobacter pyloristrains from different geographical regions and compared withconventional clustering methods. The algorithm works by firstgrouping strains that share a common minimum set of R-M systemsand gradually adds strains according to the number of the R-Msystems acquired. Dendrograms revealed a cluster of Africanstrains, which suggest that R-M systems are present in H.pylorigenome since its human host migrates from Africa. Availability: The software files are available at http://www.ff.ul.pt/paginas/jvitor/Bioinformatics/MCRM_algorithm.zip Contact: filipavale{at}fe.ucp.pt Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

GOTreePlus: an interactive gene ontology browser

Summary: We developed an interactive gene ontology (GO) browsernamed GOTreePlus that superimposes annotation information overGO structures. It can facilitate the identification of importantGO terms through interactive visualization of them in the GOstructure. The interactive pie chart summarizing an annotationdistribution for a selected GO term provides users with a succinctcontext-sensitive overview of their experimental results. Wetested our GOTreePlus using a proteome profiling dataset obtainedon differentiation of retinal pigment epithelial cells where399 proteins were quantified. Availability: http://bioinformatics.cnmcresearch.org/GOTreePlus/ Contact: jseo{at}cnmcresearch.org Associate Editor: John Quackenbush     

MHC Class II DRB Variability and Parasite Load in the Striped Mouse (Rhabdomys pumilio) in the Southern Kalahari

doi:10.1093/molbev/msi112 Mol. Biol. Evol. 22     

PlasmoGF: an integrated system for comparative genomics and phylogenetic analysis of Plasmodium gene families

Summary: Malaria, one of the world's most common diseases, iscaused by the intracellular protozoan parasite known as Plasmodium.Recently, with the arrival of several malaria parasite genomes,we established an integrated system named PlasmoGF for comparativegenomics and phylogenetic analysis of Plasmodium gene families.Gene families were clustered using the Markov Cluster algorithmimplemented in TribeMCL program and could be searched usingkeywords, gene-family information, domain composition, GeneOntology and BLAST. Moreover, a number of useful bioinformaticstools were implemented to facilitate the analysis of these putativePlasmodium gene families, including gene retrieval, annotation,sequence alignment, phylogeny construction and visualization.In the current version, PlasmoGF contained 8980 sets of genefamilies derived from six malaria parasite genomes: Plasmodium.falciparum, P. berghei, P. knowlesi, P. chabaudi, P. vivax andP. yoelii. The availability of such a highly integrated systemwould be of great interest for the community of researchersworking on malaria parasite phylogenomics. Availability: PlasmoGF is freely available at http://bioinformatics.zj.cn/pgf/ Contact: xiaokunli{at}163.net; baoqy{at}genomics.org.cn; fuz3{at}psu.edu Associate Editor: Jonathan Wren The authors wish it to be known that, in their opinion, thefirst two authors should be regarded as joint First Authors.     

Compressed suffix tree--a basis for genome-scale sequence analysis

Summary: Suffix tree is one of the most fundamental data structuresin string algorithms and biological sequence analysis. Unfortunately,when it comes to implementing those algorithms and applyingthem to real genomic sequences, often the main memory size becomesthe bottleneck. This is easily explained by the fact that whilea DNA sequence of length n from alphabet = {A, C, G, T } canbe stored in n log ||= 2n bits, its suffix tree occupies O(nlog n) bits. In practice, the size difference easily reachesfactor 50. We provide an implementation of the compressed suffix tree veryrecently proposed by Sadakane (Theory of Computing Systems,in press). The compressed suffix tree occupies space proportionalto the text size, i.e. O(n log} | |) bits, and supports alltypical suffix tree operations with at most log n factor slowdown.Our experiments show that, e.g. on a 10 MB DNA sequence, thecompressed suffix tree takes 10% of the space of normal suffixtree. Typical operations are slowed down by factor 60. Availability: The C++ implementation under GNU license is availableat http://www.cs.helsinki.fi/group/suds/cst/. An example programimplementing a typical pattern discovery task is included. Experimentalresults in this note correspond to version 0.95. Contact: vmakinen{at}cs.helsinki.fi     

ELECTROPHORETIC AND MORPHOMETRIC CHARACTERS IN POPULATION DIFERENTIATION OF THE PEARL OYSTER, PINCTADA RADIATA (LEACH), FROM AROUND BAHRAIN

Variation at the leucine aminopeptidase (Lap), glucose phosphateisomerase (Gpi) and tetrazolium oxidase (To) loci was investigatedin samples of three populations, Al-Mayana (MAY), Shigita (SH)and Mina Salman (MS), of Pinctada radiata from pearl oysterbeds around Bahrain. The To locus was monomor-phic. SignificantLap and Gpi heterozygote deficiencies were evident and it issuggested that these were generated by selection. The MS population,to the East of Bahrain, differed significantly in Gpi allelefrequencies from both Northern populations (MAY, SH) and Nei'sgenetic identity indicates a close relationship between theNorthern populations. Measurements of shell morphometrics were used both as ratiosof one dimension to another, and as regressions of one dimensionon another to examine relatedness between populations. Boththese mor-phometric approaches gave different results from eachother and also differed from the electrophoretic data. It isconcluded that estimates of relatedness in pearl oysters basedon electrophoretic data will be more reliable than those basedon shell shape. (Received 20 November 1990; accepted 12 April 1991)     

Slider--maximum use of probability information for alignment of short sequence reads and SNP detection

Motivation: A plethora of alignment tools have been createdthat are designed to best fit different types of alignment conditions.While some of these are made for aligning Illumina SequenceAnalyzer reads, none of these are fully utilizing its probability(prb) output. In this article, we will introduce a new alignmentapproach (Slider) that reduces the alignment problem space byutilizing each read base's probabilities given in the prb files. Results: Compared with other aligners, Slider has higher alignmentaccuracy and efficiency. In addition, given that Slider matchesbases with probabilities other than the most probable, it significantlyreduces the percentage of base mismatches. The result is thatits SNP predictions are more accurate than other SNP predictionapproaches used today that start from the most probable sequence,including those using base quality. Contact: nmalhis{at}bcgsc.ca Supplementary information and availability: http://www.bcgsc.ca/platform/bioinfo/software/slider Associate Editor: Dmitrij Frishman     

ERRATUM

R. MANLY. The larval development of Tricolia pullus (L.)J. moll.Stud. (1976) 42,361–369. The legends of Figs 2 and 3 shouldbe transposed.     

Interaction Between Cryopreservation, Rewarming Rate and Seed Humidification on the Germination of Two Spanish Endemic Species

The effects of humidification, storage in liquid nitrogen (1or 30 d) and rewarming rate on seed germination were studiedin two Spanish endemics. Humidification resulted in higher germinationpercentages only in the species with hard covers, especiallyin slowly rewarmed seeds. In an experiment lasting 21 weeks,seeds stored in liquid nitrogen were removed for 10 min eachweek to mimic the withdrawal of samples from a seed bank; thishad no effect on germination.Copyright 1998 Annals of BotanyCompany Centaurea hyssopifolia,Limonium dichotomum, cryopreservation, cypsela, endemics, germination, humidification, seeds.     

In silico Biochemical Reaction Network Analysis (IBRENA): a package for simulation and analysis of reaction networks

Summary: We present In silico Biochemical Reaction Network Analysis(IBRENA), a software package which facilitates multiple functionsincluding cellular reaction network simulation and sensitivityanalysis (both forward and adjoint methods), coupled with principalcomponent analysis, singular-value decomposition and model reduction.The software features a graphical user interface that aids simulationand plotting of in silico results. While the primary focus isto aid formulation, testing and reduction of theoretical biochemicalreaction networks, the program can also be used for analysisof high-throughput genomic and proteomic data. Availability: The software package, manual and examples areavailable at http://www.eng.buffalo.edu/~neel/ibrena Contact: neel{at}eng.buffalo.edu Associate Editor: Limsoon Wong     

Parasitic Wasps Learn and Report Diverse Chemicals with Unique Conditionable Behaviors

Chemical Senses, 28, 545–549 Regrettably, an error occurred in Figure 3 of this