ProPhylER: A curated online resource for protein function and structure based on evolutionary constraint analyses

  1. Jonathan Binkley1,
  2. Kalpana Karra1,
  3. Andrew Kirby2,
  4. Midori Hosobuchi1,
  5. Eric A. Stone3 and
  6. Arend Sidow1,4
  1. 1 Stanford University School of Medicine, Departments of Pathology and Genetics, Stanford, California 94305, USA;
  2. 2 Wellesley, Massachusetts 02482, USA;
  3. 3 North Carolina State University, Departments of Statistics and Genetics, Raleigh, North Carolina 27695, USA

    Abstract

    ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure are relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The “ProPhylER Interface” displays predictive analyses in sequence space; the “CrystalPainter” maps evolutionary constraints onto solved protein structures. Here we summarize ProPhylER's data content and analysis pipeline, demonstrate the use of ProPhylER's interfaces, and evaluate ProPhylER's unique regional analysis of evolutionary constraint. The high accuracy of ProPhylER's regional analysis complements the high resolution of its single-site analysis to effectively guide and inform structure–function investigations and predict the impact of polymorphisms.

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    1. Published in Advance October 21, 2009, doi: 10.1101/gr.097121.109 Genome Res. 20: 142-154 Copyright © 2010 by Cold Spring Harbor Laboratory Press

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