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Identification of Relevant Genetic Alterations in Cancer Using Topological Data Analysis
Raúl Rabadán, Yamina Mohamedi, Udi Rubin, Tim Chu, Adam N. Alghalith, Oliver Elliott, Luis Arnés, Santiago Cal, Álvaro J. Obaya, Arnold J. Levine, Pablo G. Cámara
Large-scale cancer genomic studies enable the systematic identification of mutations that lead to the genesis and progression of tumors, uncovering the underlying molecular mechanisms and potential therapies. While some such mutations are recurrently found in many tumors, many others exist solely within a few samples, precluding detection by conventional recurrence-based statistical approaches. Integrated analysis of somatic mutations and RNA expression data across 12 tumor types reveals that mutations of cancer genes are usually accompanied by substantial changes in expression. We use topological data analysis to leverage this observation and uncover 38 elusive candidate cancer-associated genes, including inactivating mutations of the metalloproteinase ADAMTS12 in lung adenocarcinoma. We show that ADAMTS12−/− mice have a five-fold increase in the susceptibility to develop lung tumors, confirming the role of ADAMTS12 as a tumor suppressor gene. Our results demonstrate that data integration through topological techniques can increase our ability to identify previously unreported cancer-related alterations., Rare cancer mutations are often missed using recurrence-based statistical approaches, but are usually accompanied by changes in expression. Here the authors leverage this information to uncover several elusive candidate cancer-associated genes using topological data analysis.
Topological Data Analysis for Genomics and Evolution: Topology in Biology
Raul Rabadan, Andrew J. Blumberg
Biology has entered the age of Big Data. A technical revolution has transformed the field, and extracting meaningful information from large biological data sets is now a central methodological challenge. Algebraic topology is a well-established branch of pure mathematics that studies qualitative descriptors of the shape of geometric objects. It aims to reduce comparisons of shape to a comparison of algebraic invariants, such as numbers, which are typically easier to work with. Topological data analysis is a rapidly developing subfield that leverages the tools of algebraic topology to provide robust multiscale analysis of data sets. This book introduces the central ideas and techniques of topological data analysis and its specific applications to biology, including the evolution of viruses, bacteria and humans, genomics of cancer, and single cell characterization of developmental processes. Bridging two disciplines, the book is for researchers and graduate students in genomics and evolutionary biology as well as mathematicians interested in applied topology.