Consensus clustering applied to multi-omics disease subtyping

Abstract

Background: Facing the diversity of omics data and the difficulty of selecting one result over all those produced by several methods, consensus strategies have the potential to reconcile multiple inputs and to produce robust results. Results: Here, we introduce ClustOmics, a generic consensus clustering tool that we use in the context of cancer subtyping. ClustOmics relies on a non-relational graph database, which allows for the simultaneous integration of both multiple omics data and results from various clustering methods. This new tool conciliates input clusterings, regardless of their origin, their number, their size or their shape. ClustOmics implements an intuitive and flexible strategy, based upon the idea of evidence accumulation clustering. ClustOmics computes co-occurrences of pairs of samples in input clusters and uses this score as a similarity measure to reorganize data into consensus clusters. Conclusion: We applied ClustOmics to multi-omics disease subtyping on real TCGA cancer data from ten different cancer types. We showed that ClustOmics is robust to heterogeneous qualities of input partitions, smoothing and reconciling preliminary predictions into high-quality consensus clusters, both from a computational and a biological point of view. The comparison to a state-of-the-art consensus-based integration tool, COCA, further corroborated this statement. However, the main interest of ClustOmics is not to compete with other tools, but rather to make profit from their various predictions when no gold-standard metric is available to assess their significance. Availability: The ClustOmics source code, released under MIT license, and the results obtained on TCGA cancer data are available on GitHub: https://github.com/galadrielbriere/ClustOmics.