PT  - JOURNAL ARTICLE
AU  - Francesco Iorio
AU  - Luz Garcia-Alonso
AU  - Jonathan Brammeld
AU  - Iñigo Martincorena
AU  - David R Wille
AU  - Ultan McDermott
AU  - Julio Saez-Rodriguez
TI  - Population-level characterization of pathway alterations with SLAPenrich dissects heterogeneity of cancer hallmark acquisition
AID  - 10.1101/077701
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 077701
4099  - http://biorxiv.org/content/early/2016/09/27/077701.short
4100  - http://biorxiv.org/content/early/2016/09/27/077701.full
AB  - We present SLAPenrich, a statistical approach implemented in an R package to search for pathways enriched for genomic alterations in large datasets. SLAPenrich mines for sample-population level enrichments, accounting for mutation rates, gene exonic lengths, and mutational mutual exclusivity. We show that SLAPenrich detects in lung adenocarcinoma pathways known to be typically altered, therapeutic targets, and associations with clinicopathological features. Finally, we explore with SLAPenrich the landscape of pathways contributing to the acquisition of the cancer hallmarks in large cohorts of patients across 10 cancer types, highlighting potential novel cancer driver genes and networks.