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ReKINect - Frequently Asked Questions

In a nutshell, what does ReKINect do?

ReKINect is a computational framework that predicts the likely functionality of mutations.

What do you mean with "likely functionality"? Can you be more specific?

ReKINect will map mutations to different functional residues and, by doing so, will not only predict how these functional residues might be affected by mutations but also propose a likely functional impact of each mutation to phosphorylation-based signaling networks (Kinases, SH2 proteins and substrates). As in any computational prediction, there might be instances where these predictions turn out to be false or to have a different effect than expected (e.g. if a given mutation is heterozygous -especially relevant for inactivations, unless there is haploinsufficiency-, or cells have adapted to a given mutation, the predicted effect might be masked). Anyhow, we still highly recommend ReKINect as a valuable source to explore potential functional mutations.

Ok, so what type of functional residues are currently been used?

We are currently mapping onto 3 different types of functional residues:

And what kind of predictions can ReKINect produce based on this mapping?

Based on this information, ReKINect can predict five mutational functionalities:

*Upstream rewiring requires NetworKIN and/or NetPhorest predictions. If you are interested in this, you can either try to run them online or get in touch with us.

For further information on ReKINect and the methodology behind our predictions, please refer to our publication (Creixell et al. submitted).

Ok, all this sounds interesting, how can I submit my sequencing results?

As illustrated below, any input file submitted to ReKINect has to follow follow what we call mutant fasta file format, where...

Illustration of the previous explanation on mutant fasta files

But my sequencing results are in vcf format. How can I generate a mutant fasta file from a vcf file?

Ideally, you (or somebody else with some degree of bioinformatics expertise) should be able to map the coordinates of every mutation in your vcf file to a unique canonical protein sequence. This can be done using ensembl's VEP service. The ProteinSeqs plugin would be particularly helpful in this case.

Why is it critical that every mutation only maps to a unique canonical protein?

In order to avoid the incorrect mapping of phosphorylation sites, ReKINect matches its large set of known phosphorylation peptides to all the reference (i.e. wild type) sequences given. Being as conservative as possible, any peptide that doesn't match any reference protein or that matches several reference proteins at the same time will be discarded. Thus, introducing several isoforms of the same protein as separate entries would lead to many phosphorylation sites being discarded from the analysis, due to them matching more than one reference sequence at the same time.

And in what format will I get my results back?

ReKINect output files contain a large amount of information for any mutation that maps onto kinases, SH2-proteins or around a phosphorylation site (Mutations not mapping onto any of these will not appear in the output file). This information is reported in one line per mutation using the following structure:

*Please note when trying to refer to columns that the numbering in the header of the output file starts from 0.

Illustration of the previous explanation on ReKINect output format

If you use ReKINect, please don't forget to cite us:
Creixell et al. Kinome-wide Decoding of Network Attacking Mutations Rewiring Cancer 2015, Cell 163, 1-16. DOI:10.1016/j.cell.2015.08.056

(C) 2013-2015 Pau Creixell and Rune Linding / Web-development: Pau Creixell and Xavier Robin

KU / BRIC / LindingLab