BEST: Bayesian estimation of species trees under the coalescent model

BEST implements a Bayesian hierarchical model to jointly estimate gene trees and the species tree from multilocus sequences. It provides a new option for estimating species phylogenies within the popular Bayesian phylogenetic program MrBayes. The technique of simulated annealing is adopted along with Metropolis coupling as performed in MrBayes to improve the convergence rate of the Markov Chain Monte Carlo algorithm. AVAILABILITY: http://www.stat.osu.edu/~dkp/BEST.     

The Synergizer service for translating gene, protein and other biological identifiers

The Synergizer is a database and web service that provides translations of biological database identifiers. It is accessible both programmatically and interactively. AVAILABILITY: The Synergizer is freely available to all users inter-actively via a web application (http://llama.med.harvard.edu/synergizer/translate) and programmatically via a web service. Clients implementing the Synergizer application programming interface (API) are also freely available. Please visit http://llama.med.harvard.edu/synergizer/doc for details.     

Accurate recognition of cis-regulatory motifs with the correct lengths in prokaryotic genomes

We present a new computational method for solving a classical problem, the identification problem of cis-regulatory motifs in a given set of promoter sequences, based on one key new idea. Instead of scoring candidate motifs individually like in all the existing motif-finding programs, our method scores groups of candidate motifs with similar sequences, called motif closures, using a P-value, which has substantially improved the prediction reliability over the existing methods. Our new P-value scoring scheme is sequence length independent, hence allowing direct comparisons among predicted motifs with different lengths on the same footing. We have implemented this method as a Motif Recognition Computer (MREC) program, and have extensively tested MREC on both simulated and biological data from prokaryotic genomes. Our test results indicate that MREC can accurately pick out the actual motif with the correct length as the best scoring candidate for the vast majority of the cases in our test set. We compared our prediction results with two motif-finding programs Cosmo and MEME, and found that MREC outperforms both programs across all the test cases by a large margin. The MREC program is available at http://csbl.bmb.uga.edu/~bingqiang/MREC1/.     

Mclip: motif detection based on cliques of gapped local profile-to-profile alignments

A multitude of motif-finding tools have been published, which can generally be assigned to one of three classes: expectation-maximization, Gibbs-sampling or enumeration. Irrespective of this grouping, most motif detection tools only take into account similarities across ungapped sequence regions, possibly causing short motifs located peripherally and in varying distance to a 'core' motif to be missed. We present a new method, adding to the set of expectation-maximization approaches, that permits the use of gapped alignments for motif elucidation. Availability: The program is available for download from: http://bioinfoserver.rsbs.anu.edu.au/downloads/mclip.jar. Supplementary information: http://bioinfoserver.rsbs.anu.edu.au/utils/mclip/info.php.     

TargetDB: a database of peptides targeting proteins to subcellular locations.

SUMMARY: TargetDB is a relational database designed to represent data on protein targeting sequences, mutant signals, subcellular targets and source organisms. AVAILABILITY: TargetDB is accessible at http://molbio.nmsu.edu:81. The web interface supports both direct data authoring and database query functions. CONTACT: moconnel@nmsu. edu, tao_wei@hms.harvard.edu     

P2BAT: a massive parallel implementation of PBAT for genome-wide association studies in R

The software tool P2BAT provides a massive parallel and user friendly implementation of the PBAT-analysis tools for family-based association tests (FBATs) in large-scale studies, including genome-wide association studies with several thousand subjects. Built on the original PBAT-implementation of the Lange-Van Steen algorithm to bypass the multiple testing problem in family-based association studies, P2BAT integrates all PBAT-analysis tools for binary and complex traits into R and makes them accessible through a user-friendly GUI. The genome-wide analysis tools are fully automated and can be ran massively parallel directly through the GUI. P2BAT is fully documented and contains graphical output tools for time-to-onset analysis. P2BAT also features the ability to test for gene and environment/drug interaction. AVAILABILITY: The P2BAT package is available as the R package 'pbatR' which can be downloaded from http://cran.r-project.org/. The PBAT-software is available at http://www.biostat.harvard.edu/~clange/.     

SNP2RFLP: a computational tool to facilitate genetic mapping using benchtop analysis of SNPs

Genome-wide analysis of single nucleotide polymorphism (SNP) markers is an extremely efficient means for genetic mapping of mutations or traits in mice. However, this approach often defines a relatively large recombinant interval. To facilitate the refinement of this interval, we developed the program SNP2RFLP. This program can be used to identify region-specific SNPs in which the polymorphic nucleotide creates a restriction fragment length polymorphism (RFLP) that can be readily assayed at the benchtop using restriction enzyme digestion of SNP-containing PCR products. The program permits user-defined queries that maximize the informative markers for a particular application. This facilitates fine-mapping in a region containing a mutation of interest, which should prove valuable to the mouse genetics community. SNP2RFLP and further details are publicly available at http://genetics.bwh.harvard.edu/snp2rflp/.     

Minimalistic Predictor of Protein Binding Energy: Contribution of Solvation Factor to Protein Binding

It has long been known that solvation plays an important role in protein-protein interactions. Here, we use a minimalistic solvation-based model for predicting protein binding energy to estimate quantitatively the contribution of the solvation factor in protein binding. The factor is described by a simple linear combination of buried surface areas according to amino-acid types. Even without structural optimization, our minimalistic model demonstrates a predictive power comparable to more complex methods, making the proposed approach the basis for high throughput applications. Application of the model to a proteomic database shows that receptor-substrate complexes involved in signaling have lower affinities than enzyme-inhibitor and antibody-antigen complexes, and they differ by chemical compositions on interfaces. Also, we found that protein complexes with components that come from the same genes generally have lower affinities than complexes formed by proteins from different genes, but in this case the difference originates from different interface areas. The model was implemented in the software PYTHON, and the source code can be found on the Shakhnovich group webpage: http://faculty.chemistry.harvard.edu/shakhnovich/software.     

DNA polymorphism detector: an automated tool that searches for allelic matches in public databases for discrepancies found in clone or cDNA sequences

SUMMARY: DNA polymorphism detector (DPD) is a new web application developed to help automate the process of cDNA clone validation. DPD identifies and highlights discrepancies between any cDNA clone sequence and its expected reference sequence. To determine if these differences correspond to natural genetic polymorphisms (versus artifacts introduced during clone production or evaluation), DPD uses the discrepancies, along with flanking sequences, to search GenBank for identical matching strings. If matching DNA sequences are found, DPD verifies that they are from the same gene. The application then reports the discrepancy as a polymorphism along with the corresponding GenBank reference information. AVAILABILITY: DPD is currently hosted by the Harvard Institute of Proteomics at http://www.hip.harvard.edu     

SNP2RFLP: a computational tool to facilitate genetic mapping using benchtop analysis of SNPs

Genome-wide analysis of single nucleotide polymorphism (SNP) markers is an extremely efficient means for genetic mapping of mutations or traits in mice. However, this approach often defines a relatively large recombinant interval. To facilitate the refinement of this interval, we developed the program SNP2RFLP. This program can be used to identify region-specific SNPs in which the polymorphic nucleotide creates a restriction fragment length polymorphism (RFLP) that can be readily assayed at the benchtop using restriction enzyme digestion of SNP-containing PCR products. The program permits user-defined queries that maximize the informative markers for a particular application. This facilitates fine-mapping in a region containing a mutation of interest, which should prove valuable to the mouse genetics community. SNP2RFLP and further details are publicly available at http://genetics.bwh.harvard.edu/snp2rflp/.

     

PCCA: a program for phylogenetic canonical correlation analysis

Summary: PCCA (phylogenetic canonical correlation analysis)is a new program for canonical correlation analysis of multivariate,continuously valued data from biological species. Canonicalcorrelation analysis is a technique in which derived variablesare obtained from two sets of original variables whereby thecorrelations between corresponding derived variables are maximized.It is a very useful multivariate statistical method for thecalculation and analysis of correlations between character sets.The program controls for species non-independence due to phylogenetichistory and computes canonical coefficients, correlations andscores; and conducts hypothesis tests on the canonical correlations.It can also compute a multivariate version of Pagel's , whichcan then be used in the phylogenetic transformation. Availability: PCCA is distributed as DOS/Windows, Mac OS X andLinux/Unix executables with a detailed program manual and isfreely available on the World Wide Web at: http://anolis.oeb.harvard.edu/~liam/programs/. Contact: lrevell{at}fas.harvard.edu Associate Editor: Keith Crandall     

GeneMerge--post-genomic analysis,data mining,and hypothesis testing

SUMMARY: GeneMerge is a web-based and standalone program written in PERL that returns a range of functional and genomic data for a given set of study genes and provides statistical rank scores for over-representation of particular functions or categories in the data set. Functional or categorical data of all kinds can be analyzed with GeneMerge, facilitating regulatory and metabolic pathway analysis, tests of population genetic hypotheses, cross-experiment comparisons, and tests of chromosomal clustering, among others. GeneMerge can perform analyses on a wide variety of genomic data quickly and easily and facilitates both data mining and hypothesis testing. AVAILABILITY: GeneMerge is available free of charge for academic use over the web and for download from: http://www.oeb.harvard.edu/hartl/lab/publications/GeneMerge.html.     

SPCalc: A web-based calculator for sample size and power calculations in micro-array studies

Calculation of the appropriate sample size in planning microarray studies is important because sample collection can be expensive and time-consuming. Sample-size calculation is also a challenging issue for microarray studies because the number of genes is far larger than the number of samples so that traditional methods of sample-size calculation cannot be directly applied. To help investigators answer the question of how many samples are needed in their microarray studies, we developed a user-friendly web-based calculator, SPCalc, for calculating sample size and power for a variety of commonly used experimental designs, including completely randomized treatmentcontrol design, matched-pairs design, multiple-treatment design having an isolated treatment effect, and randomized block design. AVAILABILITY: The web-based calculator SPCalc is publicly available at http://www.biostat.harvard.edu /people/faculty/mltlee/webfront-r.html.     

Dblox: a genome-wide test for ancient segmental duplication

Dblox and RDblox provide a simple statistical test for duplicated genomic structure; the same programs can also be used to identify putatively duplicated regions. The method focuses on ancient duplication events involving protein-coding genes. AVAILABILITY: http://www.biol.sc.edu/~austin/