Human synthetic lethal inference as potential anti-cancer target gene detection.
BACKGROUND
Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods.


RESULTS
In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates.


CONCLUSIONS
Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.
Conde-Pueyo
Nuria
N
ICREA-Complex Systems Lab, Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Dr Aiguader 88, E-08003 Barcelona, Spain. nuria.conde@upf.edu
Munteanu
Andreea
A
Solé
Ricard V
RV
Rodríguez-Caso
Carlos
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019295:Computational Biology; D030541:Databases, Genetic; D015195:Drug Design; D005804:Genes, Lethal / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics
D000970:Antineoplastic Agents