About Our Software and Server
+Overview:
++
+ The Functional Analysis through Hidden Markov Models (fathmm) software and server is is capable of predicting the functional
+ effects of protein missense mutations by combining sequence conservation within hidden Markov models (HMMs), representing the
+ alignment of homologous (orthologous and/or paralogous) 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 publications:
+
+ 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
+ 
+
+ Shihab HA, Gough J, Cooper DN, Day INM, Gaunt, TR. (2013). Predicting the Functional Consequences of Cancer-Associated Amino Acid Substitutions.
+ Bioinformatics 29:1504-1510.
+
+
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+ +
Input Format:
++
+ Our software accepts one of the following formats (see here for annotating VCF files):
+
+
+
-
+
-
+
<protein> <substitution>+
+ -
+
dbSNP rs identifiers+
+
+ In the above,
<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, RefSeq and Ensembl protein identifiers, e.g.:
+ +
+P43026 L441P ++ or: +
+
+rs137854462 ++ +
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+ +
Batch Submission:
++
+
+ It is possible to submit multiple amino acid substitutions as a 'Batch Submission' via our server. Here, all amino acid substitutions for a protein can be
+ entered on a single line and should be separated by a comma, e.g:
+
+
+P43026 L441P +ENSP00000325527 N548I,E1073K,C2307S ++
+ Note: this option is not available when analysing dbSNP rs identifiers. + +
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+ +
VCF Annotation:
++
+ 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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+ +