The APPRIS annotation pipeline deploys a range of computational methods to provide value to the annotations of the human genome. The server flags variants that code for proteins with altered structure, function or localization, and exons that are evolving in a non-neutral fashion. APPRIS also selects one of the CDS for each gene as the principal functional isoform. The pipeline is made up of separate modules that combine protein structure and function information and evolutionary evidence. Each module has been implemented as a separate web service.
firestar (Lopez et al. 2007 (link), 2011 (link)) is a method that predicts functionally important residues in protein sequences.
Matador3D is locally installed and checks for structural homologs for each transcript in the PDB (Berman et al. 2000 (link)).
SPADE uses a locally installed version of the program Pfamscan (Finn et al. 2010 (link)) to identify the conservation of protein functional domains.
INERTIA detects exons with non-neutral evolutionary rates. Transcripts are aligned against related species using three different alignment methods, Kalign (Lassmann and Sonnhammer 2005 (link)), multiz (Blanchette et al. 2004 (link)), and PRANK (Loytynoja and Goldman 2005 (link)), and evolutionary rates of exons for each of the three alignments are contrasted using SLR (Massingham and Goldman 2005 (link)).
CRASH makes conservative predictions of signal peptides and mitochondrial signal sequences by using locally installed versions of the SignalP and TargetP programs (Emanuelsson et al. 2007 (link)) .
THUMP makes conservative predictions of trans-membrane helices by analyzing the output of three locally installed trans-membrane prediction methods, MemSat (Jones 2007 (link)), PRODIV (Viklund and Elofsson 2004 (link)), and PHOBIUS (Kall et al. 2004 (link)).
CExonic is a locally developed method that uses exonerate (Slater and Birney 2005 (link)) to align mouse and human transcripts and then looks for patterns of conservation in exonic structure.
CORSAIR is a locally installed method that checks for orthologs for each variant in a locally installed vertebrate protein sequence database.
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Harrow J., Frankish A., Gonzalez J.M., Tapanari E., Diekhans M., Kokocinski F., Aken B.L., Barrell D., Zadissa A., Searle S., Barnes I., Bignell A., Boychenko V., Hunt T., Kay M., Mukherjee G., Rajan J., Despacio-Reyes G., Saunders G., Steward C., Harte R., Lin M., Howald C., Tanzer A., Derrien T., Chrast J., Walters N., Balasubramanian S., Pei B., Tress M., Rodriguez J.M., Ezkurdia I., van Baren J., Brent M., Haussler D., Kellis M., Valencia A., Reymond A., Gerstein M., Guigó R, & Hubbard T.J. (2012). GENCODE: The reference human genome annotation for The ENCODE Project. Genome Research, 22(9), 1760-1774.
Publication 2012
Evolutionary Exonic Gene Helices Human Human genome Isoform Membrane Mitochondrial Mouse Neutral evolutionary Protein Protein domains Protein sequences Protein variant Signal sequences Vertebrate
Corresponding Organization :
Other organizations :
Wellcome Sanger Institute, University of California, Santa Cruz, Massachusetts Institute of Technology, University of Lausanne, Centre for Genomic Regulation, Yale University, Spanish National Cancer Research Centre, Center for Systems Biology
Computational methods used in the APPRIS annotation pipeline
dependent variables
Annotations of the human genome
Identification of variants that code for proteins with altered structure, function or localization
Identification of exons that are evolving in a non-neutral fashion
Selection of the principal functional isoform for each gene
control variables
Not explicitly mentioned
controls
No positive or negative controls specified
Annotations
Based on most similar protocols
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