Interpreting personal transcriptomes: personalized mechanism-scale profiling of RNA-seq data

Pac Symp Biocomput. 2013:159-70.

Abstract

Despite thousands of reported studies unveiling gene-level signatures for complex diseases, few of these techniques work at the single-sample level with explicit underpinning of biological mechanisms. This presents both a critical dilemma in the field of personalized medicine as well as a plethora of opportunities for analysis of RNA-seq data. In this study, we hypothesize that the "Functional Analysis of Individual Microarray Expression" (FAIME) method we developed could be smoothly extended to RNA-seq data and unveil intrinsic underlying mechanism signatures across different scales of biological data for the same complex disease. Using publicly available RNA-seq data for gastric cancer, we confirmed the effectiveness of this method (i) to translate each sample transcriptome to pathway-scale scores, (ii) to predict deregulated pathways in gastric cancer against gold standards (FDR<5%, Precision=75%, Recall =92%), and (iii) to predict phenotypes in an independent dataset and expression platform (RNA-seq vs microarrays, Fisher Exact Test p<10(-6)). Measuring at a single-sample level, FAIME could differentiate cancer samples from normal ones; furthermore, it achieved comparative performance in identifying differentially expressed pathways as compared to state-of-the-art cross-sample methods. These results motivate future work on mechanism-level biomarker discovery predictive of diagnoses, treatment, and therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Computational Biology
  • Data Interpretation, Statistical
  • Databases, Nucleic Acid / statistics & numerical data
  • Humans
  • Models, Statistical
  • Oligonucleotide Array Sequence Analysis / statistics & numerical data
  • Precision Medicine / statistics & numerical data*
  • RNA, Neoplasm / genetics
  • ROC Curve
  • Sequence Analysis, RNA / statistics & numerical data*
  • Stomach Neoplasms / genetics
  • Transcriptome*

Substances

  • RNA, Neoplasm