Using singscore to predict mutation status in acute myeloid leukemia from transcriptomic signatures

F1000Res. 2019 Jun 3:8:776. doi: 10.12688/f1000research.19236.3. eCollection 2019.

Abstract

Advances in RNA sequencing (RNA-seq) technologies that measure the transcriptome of biological samples have revolutionised our ability to understand transcriptional regulatory programs that underpin diseases such as cancer. We recently published singscore - a single sample, rank-based gene set scoring method which quantifies how concordant the transcriptional profile of individual samples are relative to specific gene sets of interest. Here we demonstrate the application of singscore to investigate transcriptional profiles associated with specific mutations or genetic lesions in acute myeloid leukemia. Using matched genomic and transcriptomic data available through the TCGA we show that scoring of appropriate signatures can distinguish samples with corresponding mutations, reflecting the ability of these mutations to drive aberrant transcriptional programs involved in leukemogenesis. We believe the singscore method is particularly useful for studying heterogeneity within a specific subsets of cancers, and as demonstrated, we show the ability of singscore to identify where alternative mutations appear to drive similar transcriptional programs.

Keywords: AML mutations; NPM1c mutation; TCGA; gene set scoring; mutation prediction; signature scoring; single sample.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Forecasting
  • Genomics
  • Humans
  • Leukemia, Myeloid, Acute*
  • Mutation*
  • Sequence Analysis, RNA
  • Transcriptome*

Grants and funding

This work was partially supported by the National Health and Medical Research Council (NHMRC) Project Grant APP1128609. MJD was supported by the NBCF Career Development Fellowship ECF-14-043 and the Betty Smyth Centenary Fellowship in Bioinformatics.