Release
ProPhylER 1.0 is live now.
News
January 5 2010
The ProPhylER paper is now published in Genome Research
March 12 2010
Searching by name is now supported on the search page
March 12 2010
Searching with hg 18 coordinates for evaluating coding SNPs is now supported
Contacts
prophyler [at] prophyler.org
arend [at] stanford.edu
Resource Links
Ensembl
Uniprot
PDB
WuBlast
Probcons
Semphy
Jmol
Java
Other Links
Sidow Lab
Stanford Pathology Dept
Stanford Genetics Dept
Stanford School of Medicine
Funded by
Visual Explanations of Key ProPhylER Concepts
You know what orthologs are ... or do you? And what exactly is "substitutions per site", and why should you care? In this section, these and other key ProPhylER concepts are explained.
Your Protein in the Context of Trees
Together with the underlying sequence alignments, phylogenetic trees form the basis for ProPhylER's analyses. Trees model evolutionary relationships between sequences. In this slide show, you learn about trees and how ProPhylER treats the complex hierarchical relationships of sequences that result from evolutionary processes.
Go to Tree slide show in a separate window.
Download the powerpoint file (higher quality).
Evolution-Structure-Function Analyses
This html slide show explains ESF analyses. It will answer questions such as "How are the plots generated?" and "What is constraint?" More in-depth explanations can be found in the original ESF paper <pdf, 0.5MB>, though it is important to bear in mind that we have changed some of the methodology since that paper was published. The concepts have not changed.
Go to ESF analysis slide show in a separate window.
Download the powerpoint file (higher quality).
Physicochemical Constraint Plots and Alignment Summaries
The concept is simple: an alignment contains more information about physicochemical constraints than a single sequence. This html slide show explains how ProPhylER leverages phylogenetic information to calculate alignment summaries and physicochemical profiles.
Go to Physicochemical Profile and Alignment Summary slide show in a separate window.
Download the powerpoint file (higher quality).
Multivariate Analysis of Protein Polymorphism
This html slide show explains the MAPP methodology. MAPP, by contrast to ESF which yields regional features, focuses on single positions, and on all possible substitutions in them. If this concept slide show isn't enough, read the original MAPP paper <pdf, 0.8MB>.
Go to MAPP slide show in a separate window.
Download the powerpoint file (higher quality).
MAPP vs ESF
MAPP and ESF analyses serve distinct goals, but they are complementary. You may first want to find the most important ECRs (with ESF analysis) and then decide which specific positions or replacements to focus on using MAPP. Similarly, you might be interested in whether a naturally occurring mutation affects a position in an ECR (which the ESF profile will tell you) and whether the mutation is likely to be deleterious (for which the MAPP track will be informative).
Sample Applications of ProPhylER Analyses
In this paper (pdf, 0.5MB), ESF results aid in the functional analysis of a novel protein.
In this example of ESF analyses (pdf, 1.2MB), a functional divergence between paralogs is analyzed.
This paper (pdf, 0.4MB) uses ESF in conjunction with physicochemical profiles.
ProPhylER Paper
Here is a pdf of the 2010 Genome Research ProPhylER paper (Binkley et al).ProPhylER Dataflow
Alignments, trees, and results from ESF Analyses and MAPP are all precomputed by the dataflow whose main features and concepts are described in this set of pages.
Last updated 1/11/10