What is wKinMut?
wKinMut is an integrated framework for the analysis of kinase mutations. The objective of this framework is to help in the interpretation of the consequences of mutations in the protein kinase superfamily on protein structure and function, and their relationship with disease and cancer.
It displays information from diverse sources, that include:
- Protein/Gene general information from Gene Ontology
- Domain information from PFAM
- Structural information from PDB
- Predictions of mutation pathogenicity (KinMut, SIFT)
- Information from mutation databases (Uniprot Variant Pages, Kinmutbase, SAAPdb, COSMIC) and genotyping projects
- Mutation mentions from the literature (SNP2L)
- Protein Protein Interactions extracted from the literature (iHOP)
How does wKinMut predict the impact of the kinase mutations?
We associate a number sequence-derived features to disease-associated kinase mutations, including: a) at the gene level, the membership to a Kinbase group and Gene Ontology terms. b) at the domain level, the occurrence of the mutation inside a PFAM domain, and c) at the residue level, several properties including amino acid type, functional annotations from Swissprot and FireDB, specificity-determining positions, etc. We examined the independent significance of these properties and their combination with a Support Vector Machine (SVM). An SVM score greater than -0.5 indicates the mutation is pathogenic.
Is there a quick tutorial to get the grips with wKinMut?
Yes, indeed. Here is the quick reference tutorial of the predictor. Tutorial
In which format should I submit the mutations?
The wKinMut submission format includes the Uniprot/Swissprot accession number, the wild type residue, the position and the mutated residue. For instance, a mutation from Glycine to Alanine in position 719 of the Epidermal Growth factor receptor, will be encoded P00533 G719A. Multiple mutations can be submitted at a time, either as a file (one mutation per line) or via the applications form.
Is there any sample dataset I can use to try wKinMut?
Yes, there is. In the framework's main page, press 'autofill example' to load a toy dataset or download a 'sample file' that can be used with wKinMut.
My protein is not a kinase. Will wKinMut work?
No. Since some of the features are kinase-specific we can only provide results within the framework of the protein-kinase superfamily. For other protein families we recommend you refer to other genome-wide servers: SNAP, Polyphen, SNPs&GO, etc.
How do I get extended information about the mutations?
In the results table, click on 'View' in the right-most 'Details' column. This will redirect you to a new page containing information including the values of the features using for classification, Protein-Protein information, mentions in the literature of the mutation and existing records of the mutation in other databases. This additional information is intended to provide the basic background to help to understand and interpret the consequences of the mutations.
What shall I do if Jmol plugging does not display the structures (Mac OS Lion and Mountain Lion)?
We have tested the Jmol plugging in different platforms and browsers and it works smoothly in most of them. However, some users of the recent Mac OS versions (Lion and Mountain Lion) will have to make sure that a) the Java Virtual Machine, which used to be installed by default in other Mac OSs, has been actively installed on their computers and b) that they Jmol plugging has been granted access to run. We suggest that the "Always run on this computer" option is chosen so that persistent permission is granted.
Where does the Protein-Protein Interaction information come from?
Protein-Protein Interactions (PPI) information comes from iHOP. iHOP is a powerful text mining system to automatically extract protein protein interactions from PubMed abstracts. In addition, the original paper sentences are also provided as a means to relate the interaction information with its context.
Where does the Literature Information come from?
The sentences providing contextual information about the mutations come directly from the literature. We obtain this information using SNP2L. In brief, SNP2L is a literature mining pipeline for the automatic extraction and disambiguation of single-point mutation mentions from both abstracts as well as full text articles, followed by a sequence validation check to link mutations to their corresponding kinase protein sequences.
Which databases are revised in order to gather information about the mutations?
Currently, four different databases are revised: Uniprot Variation Pages, COSMIC, SAAPdb and KinMutBase. These databases were selected in order to cover different aspects of human protein kinase mutation.
Can I access wKinMut programmatically?
Yes. The predictions from KinMut can be downloaded programmatically using a REST service. An example can be found here
How should I cite KinMut or wKinMut?
Izarzugaza JM, del Pozo A, Vazquez M, Valencia A. Prioritization of pathogenic mutations in the protein kinase superfamily. BMC Genomics. 2012 Jun 18;13 Suppl 4:S3. doi: 10.1186/1471-2164-13-S4-S3. PubMed PMID: 22759651
I have a question about wKinMut that is NOT in this help section. May I contact you?
Of course you can. Feel free to email us (txema-at-cbs-dot-dtu-dot-dk or miguel-dot-vazquez-at-cnio-dot-es) and we will try to solve your doubts.