From dfb6b48dc3343144c2a8239a2a0d8056c280aa91 Mon Sep 17 00:00:00 2001 From: Hashem Ali Shihab Date: Fri, 22 Mar 2013 10:29:39 +0000 Subject: [PATCH] Cosmetic Changes --- cancer.html | 24 ++-- css/fathmm.css | 5 +- index.html | 12 +- inherited.html | 352 +++++++++++++++++++++++++++++++------------------ 4 files changed, 250 insertions(+), 143 deletions(-) diff --git a/cancer.html b/cancer.html index 0e0ad4c..e8fb124 100755 --- a/cancer.html +++ b/cancer.html @@ -1,4 +1,8 @@ + + + + fathmm - Analyze Cancer-Associated Variants @@ -116,7 +120,7 @@

Analyze Cancer-Associated Variants

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Analyze Cancer-Associated Variants

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VCF Annotation:

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VCF Annotation:

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Analyze dbSNP/Protein Missense Variants

Obtain instant predictions for the functional, molecular and phenotypic consequences of protein missense variants.

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Enter Your Mutations:

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Enter Your Mutations:

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Overview:

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+ Our algorithm is capable of predicting the functional effects of cancer-associated protein missense mutations by combining + sequence conservation within hidden Markov models (HMMs), representing the alignment of homologous sequences and conserved + protein domains, with "pathogenicity weights", representing the overall tolerance of the corresponding model to mutations. +

+ For more information, please refer to the following publication: +

+ Shihab HA, Gough J, Cooper DN, Stenson PD, Barker GLA, Edwards KJ, Day INM, Gaunt, TR. (2013). Predicting the Functional, Molecular and Phenotypic + Consequences of Amino Acid Substitutions using Hidden Markov Models. Hum. Mutat., 34, 57-65 + fathmm Paper +

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Input Format:

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+ Our server accepts one of the following formats (see here for annotating VCF files): + +

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  • + <protein> <substitution> +
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+ Where <protein> is the protein identifier and <substitution> is the amino acid substitution in the conventional one + letter format. At present, our server accepts SwissProt/TrEMBL and Ensembl protein identifiers - multiple amino acid substitutions + can be entered on a single line and should be separated by a comma, e.g: +

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+P43026 L441P
+ENSP00000325527 N548I,E1073K,C2307S 
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  • + dbSNP rs identifiers +
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+ At present, our server accepts dbSNP v.137 annotations (we are working towards incorporating other versions of dbSNP into our database) - multiple dbSNP + identifiers should be entered on separate lines, e.g.: +

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+rs137854462
+rs28936683
+rs121908258
+rs17882252
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Prediction Algorithm:

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+ As described in our paper, our software is comprised of two algorithms: one sequence/conservation based (Unweighted) and the other + amalgamates our Unweighted algorithm with pathogenicity weights (Weighted). In short, our Weighted algorithm is capable of adjusting + our predictions to account for the tolerance of related sequences to mutations. For example, mutations falling within + diverse regions of the Cellular Tumor Antigen P53 can be weighted according to the important role the protein plays in cell regulation. + In contrast, mutations falling within conserved regions of the MHC Antigen-Regognition Domain can be down-weighted according the + hypervariable nature of the domain. +

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Phenotype Associations:

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+ Our software not only predicts the potentially deleterious nature of protein variants but it is also capable of annotating + the molecular and phenotypic consequences of these mutations via domain-centric ontologies (dcGO). + Here, the molecular consequences of mutations are statistically inferred by mapping SUPERFAMILY + domains onto the Gene Ontology, the Human Phenotype Ontology and the Mammalian Phenotype Ontology (and more). +

+ For more information on these mappings, please refer to the following publications: +

+ Fang H, Gough J. (2012). dcGO: database of domain-centric ontologies on functions, phenotypes, diseases and more. Nucleic Acids Res., 41, D536-544. +

+ Gough J, Karplus K, Hughey R, Chothia C. (2001). Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J. Mol. Biol., 313, 903-919. +

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VCF Annotation:

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+ Unfortunately, due to disk space constraints, we are unable to annotate Variant Call Format (VCF) files on your behalf. However, the consequences of all VCF variants + can be derived using the Ensembl Variant Effect Predictor (VEP). + Once annotated, the following script (available here) is capable of parsing these annotations and will provide you with a list of protein + consequences which can then be used as input into our server/software. +

+ Additional help on using our script is available by typing the following command: + 

python parseVCF.py --help
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