USNAP: fast unique dense region detection and its application to lung cancer

Author:

Wong Serene W H1ORCID,Pastrello Chiara1ORCID,Kotlyar Max1ORCID,Faloutsos Christos2,Jurisica Igor134

Affiliation:

1. Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, 60 Leonard Avenue , Toronto, ON M5T 0S8, Canada

2. Department of Computer Science, GHC 7003 Carnegie, Mellon University, 5000 Forbes Avenue , Pittsburgh, PA 15213-3891, United States

3. Departments of Medical Biophysics and Computer Science, University of Toronto , Toronto, ON, Canada

4. Institute of Neuroimmunology, Slovak Academy of Sciences , Bratislava, Slovakia

Abstract

Abstract Motivation Many real-world problems can be modeled as annotated graphs. Scalable graph algorithms that extract actionable information from such data are in demand since these graphs are large, varying in topology, and have diverse node/edge annotations. When these graphs change over time they create dynamic graphs, and open the possibility to find patterns across different time points. In this article, we introduce a scalable algorithm that finds unique dense regions across time points in dynamic graphs. Such algorithms have applications in many different areas, including the biological, financial, and social domains. Results There are three important contributions to this manuscript. First, we designed a scalable algorithm, USNAP, to effectively identify dense subgraphs that are unique to a time stamp given a dynamic graph. Importantly, USNAP provides a lower bound of the density measure in each step of the greedy algorithm. Second, insights and understanding obtained from validating USNAP on real data show its effectiveness. While USNAP is domain independent, we applied it to four non-small cell lung cancer gene expression datasets. Stages in non-small cell lung cancer were modeled as dynamic graphs, and input to USNAP. Pathway enrichment analyses and comprehensive interpretations from literature show that USNAP identified biologically relevant mechanisms for different stages of cancer progression. Third, USNAP is scalable, and has a time complexity of O(m+mc log nc+nc log nc), where m is the number of edges, and n is the number of vertices in the dynamic graph; mc is the number of edges, and nc is the number of vertices in the collapsed graph. Availability and implementation The code of USNAP is available at https://www.cs.utoronto.ca/~juris/data/USNAP22.

Funder

Ontario Research Fund

Natural Sciences and Engineering Research Council of Canada

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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