ViLoN—a multi-layer network approach to data integration demonstrated for patient stratification

Author:

Kańduła Maciej M12ORCID,Aldoshin Alexander D1,Singh Swati13,Kolaczyk Eric D4,Kreil David P1ORCID

Affiliation:

1. Institute of Molecular Biotechnology, Boku University Vienna , Austria

2. Janssen Pharmaceutica NV , Beerse, Belgium

3. Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur , Kanpur, India

4. Department of Mathematics and Statistics, McGill University , Canada

Abstract

AbstractWith more and more data being collected, modern network representations exploit the complementary nature of different data sources as well as similarities across patients. We here introduce the Variation of information fused Layers of Networks algorithm (ViLoN), a novel network-based approach for the integration of multiple molecular profiles. As a key innovation, it directly incorporates prior functional knowledge (KEGG, GO). In the constructed network of patients, patients are represented by networks of pathways, comprising genes that are linked by common functions and joint regulation in the disease. Patient stratification remains a key challenge both in the clinic and for research on disease mechanisms and treatments. We thus validated ViLoN for patient stratification on multiple data type combinations (gene expression, methylation, copy number), showing substantial improvements and consistently competitive performance for all. Notably, the incorporation of prior functional knowledge was critical for good results in the smaller cohorts (rectum adenocarcinoma: 90, esophageal carcinoma: 180), where alternative methods failed.

Funder

Austrian Marshall Plan Foundation

Janssen Pharmaceutica NV

Publisher

Oxford University Press (OUP)

Subject

Genetics

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