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RPHAST

Siepel Lab

Major Programs

phastCons: Conservation scoring and identification of conserved elements

phastOdds: Log-odds scoring for phylogenetic models or phylo-HMMs

phyloFit: Fitting of phylogenetic models to aligned DNA sequences

phyloP: Computation of p-values for conservation or acceleration, either lineage-specific or across all branches

exoniphy: Phylogenetic exon prediction

dless: Prediction of elements under lineage-specific selection

prequel: Probabilistic reconstruction of ancestral sequences

phastBias:Identification of GC-biased gene conversion using a phylo-HMM

Utilities

Alignments: maf_parse, msa_view, msa_split, msa_diff

Phylogenetic models: tree_doctor, all_dists, draw_tree, consEntropy, indelFit, indelHistory

Sampling/bootstrapping: base_evolve, phyloBoot

Annotations: refeature, clean_genes, eval_predictions

...and others

Contact

Send feedback to: phast-help-l@cornell.edu

Background

The core libraries for PHAST and several initial programs (including phyloFit, exoniphy, and phastCons) were developed between 2002 and 2004 as part of Adam Siepel's dissertation work in David Haussler's group at UC Santa Cruz. Since that time, several new programs have been added, various improvements to the libraries have been made, and the user base has gradually expanded from a small group of close collaborators to several hundred people with diverse research interests. As of 2006, the project has moved to the Siepel Lab at Cornell, with development and maintenance continuing in collaboration with Katie Pollard's lab at UC San Francisco. Since 2008, Melissa Hubisz has been the lead programmer working on PHAST and RPHAST. The PHAST/RPHAST project now has dedicated funding from the National Science Foundation and National Institutes of Health (see Funding).

Acknowledgments

A number of collaborators have helped to improve PHAST during the course of its development. In particular, Elliott Margulies (NHGRI) was a devoted and patient user early in the project, and his constructive feedback led to a number of new features, bug fixes, and other improvements. Valuable feedback has also come from Kate Rosenbloom and Hiram Clawson (UCSC), and James Taylor (previously Penn State, now Emory U.). Katie Pollard has contributed to the theory behind the dless and phyloP programs, and has also made many valuable suggestions for features and bug fixes.

Open Source

From 2004-2007, PHAST was freely available for academic use, by email request, but the right to license it for a fee for commercial use had been reserved (at the advice of the UC administration). As of 2008, the package is fully open source, and is available for download from these pages under the terms of a BSD-style license.

References

The following publications detail methods implemented in PHAST. For applications of the software see complete list of publications.

  1. Siepel A and Haussler D. Combining phylogenetic and hidden Markov models in biosequence analysis. Proc. 7th Int'l Conf. on Research in Computational Molecular Biology (RECOMB '03), pp. 277-286, 2003 [reprint]. Later published in a slightly revised form: J Comput Biol 11:413-428, 2004. [reprint]

  2. Siepel A and Haussler D. Phylogenetic estimation of context-dependent substitution rates by maximum likelihood. Mol Biol Evol 21:468-488, 2004.

  3. Siepel A and Haussler D. Computational identification of evolutionarily conserved exons. Proc. 8th Int'l Conf. on Research in Computational Molecular Biology, pp. 177-186, 2004. [reprint]

  4. Siepel A and Haussler D. Phylogenetic hidden Markov models. In R. Nielsen, editor, Statistical Methods in Molecular Evolution, pp. 325-351, Springer, New York, 2005. [reprint]

  5. Siepel A, Bejerano G, Pedersen JS, Hinrichs A, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, and Haussler D. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15:1034-1050, 2005.

  6. Siepel A, Pollard KS, and Haussler D. New methods for detecting lineage-specific selection. In Proceedings of the 10th International Conference on Research in Computational Molecular Biology (RECOMB 2006), pp. 190-205. [reprint] [full version]

  7. Pollard KS, Hubisz MJ, Rosenboom K, Siepel A. Detection of non-neutral substitution rates on Mammalian phylogenies. Genome Res 20:110-121, 2010.

  8. Hubisz MJ, Pollard KS, Siepel A. PHAST and RPHAST: Phylogenetic Analysis with Space/Time Models. Briefings in Bioinfomatics 12(1):41-51, 2011.

Our newest paper (Hubisz et al., Briefings in Bioinformatics, 2011) will be the preferred citation for general use of PHAST. For phastCons, please cite Siepel et al., Genome Res, 2005, for phyloFit, cite Siepel and Haussler, Mol Biol Evol, 2004, for exoniphy cite Siepel and Haussler, RECOMB, 2004, for phyloP cite Pollard et al, Genome Res, 2010, and for dless, cite Siepel, Pollard, and Haussler, RECOMB 2006.