LARVA

Large-scale Analysis of Variants in noncoding Annotations


LARVA is a computational framework designed to facilitate the study of noncoding variants. It addresses issues that have made it difficult to derive an accurate model of the background mutation rates of noncoding elements in cancer genomes. These issues include limited noncoding functional annotation, great mutation heterogeneity, and potential mutation correlations between neighboring sites. As a result, there is substantial overdispersion in the mutation count of noncoding elements.

LARVA integrates a comprehensive set of noncoding functional elements, modeling their mutation count with a beta-binomial distribution to handle overdispersion. Moreover, LARVA uses regional genomic features such as replication timing to better estimate local mutation rates and mutational enrichments.


LARVA source code

This zip archive contains LARVA's source code. This software counts variant intersections with annotations, and estimates the significance of highly mutated annotations with a beta-binomial distribution model of variant counts. The data context files below must be downloaded in order to use LARVA. See this README for details.
LARVA regression suite
This zip archive contains a regression test suite for correctness verification of LARVA. Must be placed in the same directory as the "code" folder above. See this README for details.

LARVA Data Context

This zip archive contains LARVA's data context, which must be downloaded and used with the code in order to run LARVA.

LARVA noncoding annotations

This zip archive contains the complete set of noncoding annotations collected for our LARVA analysis. See this README for details.

LARVA paper p-values

This zip archive contains the output of LARVA for our paper "LARVA: an integrative framework for Large-scale Analysis of Recurrent Variants in noncoding Annotations" currently under review for publication in Nucleic Acids Research. Each class of noncoding annotations was intersected with the variants of 760 whole cancer genomes, and LARVA was used to determine significant highly mutated annotations. See this README for details.

LARVA Docker image

This is a Dockerized version of LARVA. The included tar file can be loaded into a local Docker installation, bypassing the need to install software dependencies before using LARVA itself. See this README for details.