OncoSimulR

This package provides functions and routines for supervised analyses of mutational signatures (i.e., the signatures have to be known, cf. L. Alexandrov et al., Nature 2013 and L. Alexandrov et al., Bioaxiv 2018). In particular, the family of functions LCD (LCD = linear combination decomposition) can use optimal signature-specific cutoffs which takes care of different detectability of the different signatures. Moreover, the package provides different sets of mutational signatures, including the COSMIC and PCAWG SNV signatures and the PCAWG Indel signatures; the latter infering that with YAPSA, the concept of supervised analysis of mutational signatures is extended to Indel signatures. YAPSA also provides confidence intervals as computed by profile likelihoods and can perform signature analysis on a stratified mutational catalogue (SMC = stratify mutational catalogue) in order to analyze enrichment and depletion patterns for the signatures in different strata.

Uses quadratic programming for signature refitting, i.e., to decompose the mutation catalog from an individual tumor sample into a set of given mutational signatures (either Alexandrov-model signatures or Shiraishi-model signatures), computing weights that reflect the contributions of the signatures to the mutation load of the tumor.

Mutational signatures are carcinogenic exposures or aberrant cellular processes that can cause alterations to the genome. We created musicatk (MUtational SIgnature Comprehensive Analysis ToolKit) to address shortcomings in versatility and ease of use in other pre-existing computational tools. Although many different types of mutational data have been generated, current software packages do not have a flexible framework to allow users to mix and match different types of mutations in the mutational signature inference process. Musicatk enables users to count and combine multiple mutation types, including SBS, DBS, and indels. Musicatk calculates replication strand, transcription strand and combinations of these features along with discovery from unique and proprietary genomic feature associated with any mutation type. Musicatk also implements several methods for discovery of new signatures as well as methods to infer exposure given an existing set of signatures. Musicatk provides functions for visualization and downstream exploratory analysis including the ability to compare signatures between cohorts and find matching signatures in COSMIC V2 or COSMIC V3.

The CNVMetrics package calculates similarity metrics to facilitate copy number variant comparison among samples and/or methods. Similarity metrics can be employed to compare CNV profiles of genetically unrelated samples as well as those with a common genetic background. Some metrics are based on the shared amplified/deleted regions while other metrics rely on the level of amplification/deletion. The data type used as input is a plain text file containing the genomic position of the copy number variations, as well as the status and/or the log2 ratio values. Finally, a visualization tool is provided to explore resulting metrics.

This package compares genomic positions and genomic ranges from multiple experiments to extract common regions. The size of the analyzed region is adjustable as well as the number of experiences in which a feature must be present in a potential region to tag this region as a consensus region. In genomic analysis where feature identification generates a position value surrounded by a genomic range, such as ChIP-Seq peaks and nucleosome positions, the replication of an experiment may result in slight differences between predicted values. This package enables the conciliation of the results into consensus regions.

The qsvaR package contains functions for removing the effect of degration in rna-seq data from postmortem brain tissue. The package is equipped to help users generate principal components associated with degradation. The components can be used in differential expression analysis to remove the effects of degradation.