Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non–Small-Cell Lung Cancer Data Set

Author:

Schmidt Stephanie T.1ORCID,Akhave Neal2,Knightly Ryan E.1ORCID,Reuben Alexandre2ORCID,Vokes Natalie2ORCID,Zhang Jianhua3,Li Jun3,Fujimoto Junya4,Byers Lauren A.2ORCID,Sanchez-Espiridion Beatriz5,Diao Lixia6,Wang Jing6ORCID,Federico Lorenzo7,Forget Marie-Andree7,McGrail Daniel J.8ORCID,Weissferdt Annikka9ORCID,Lin Shiaw-Yih8,Lee Younghee4,Suzuki Erika1,Kovacs Jeffrey J.1ORCID,Behrens Carmen2,Wistuba Ignacio I.4,Futreal Andrew3,Vaporciyan Ara9,Sepesi Boris9ORCID,Heymach John V.2ORCID,Bernatchez Chantale4ORCID,Haymaker Cara4ORCID,Cascone Tina2ORCID,Zhang Jianjun2ORCID,Bristow Christopher A.1,Heffernan Timothy P.1ORCID,Negrao Marcelo V.2,Gibbons Don L.210ORCID,

Affiliation:

1. TRACTION Platform, Division of Therapeutics Discovery, The University of Texas MD Anderson Cancer Center, Houston, TX

2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

3. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

4. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

5. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX

6. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

7. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

8. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

9. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

10. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract

PURPOSE Advances in biological measurement technologies are enabling large-scale studies of patient cohorts across multiple omics platforms. Holistic analysis of these data can generate actionable insights for translational research and necessitate new approaches for data integration and mining. METHODS We present a novel approach for integrating data across platforms on the basis of the shared nearest neighbors algorithm and use it to create a network of multiplatform data from the immunogenomic profiling of non–small-cell lung cancer project. RESULTS Benchmarking demonstrates that the shared nearest neighbors-based network approach outperforms a traditional gene-gene network in capturing established interactions while providing new ones on the basis of the interplay between measurements from different platforms. When used to examine patient characteristics of interest, our approach provided signatures associated with and new leads related to recurrence and TP53 oncogenotype. CONCLUSION The network developed offers an unprecedented, holistic view into immunogenomic profiling of non–small-cell lung cancer, which can be explored through the accompanying interactive browser that we built.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

General Medicine

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