PathWalks: identifying pathway communities using a disease-related map of integrated information

Author:

Karatzas Evangelos1,Zachariou Margarita23,Bourdakou Marilena M24,Minadakis George23,Oulas Anastasis23,Kolios George4,Delis Alex1,Spyrou George M23

Affiliation:

1. Department of Informatics and Telecommunications, University of Athens, Athens 15703, Greece

2. Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus

3. The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus

4. Department of Medicine, Laboratory of Pharmacology, Democritus University of Thrace, Komotini, Greece

Abstract

Abstract Motivation Understanding the underlying biological mechanisms and respective interactions of a disease remains an elusive, time consuming and costly task. Computational methodologies that propose pathway/mechanism communities and reveal respective relationships can be of great value as they can help expedite the process of identifying how perturbations in a single pathway can affect other pathways. Results We present a random-walks-based methodology called PathWalks, where a walker crosses a pathway-to-pathway network under the guidance of a disease-related map. The latter is a gene network that we construct by integrating multi-source information regarding a specific disease. The most frequent trajectories highlight communities of pathways that are expected to be strongly related to the disease under study. We apply the PathWalks methodology on Alzheimer's disease and idiopathic pulmonary fibrosis and establish that it can highlight pathways that are also identified by other pathway analysis tools as well as are backed through bibliographic references. More importantly, PathWalks produces additional new pathways that are functionally connected with those already established, giving insight for further experimentation. Availability and implementation https://github.com/vagkaratzas/PathWalks. Supplementary information Supplementary data are available at Bioinformatics online.

Funder

National and Kapodistrian University of Athens

State Scholarships Foundation

European Social Fund

ESF

Greek State

Greece and the European Union

European Social Fund- ESF

Operational Programme «Human Resources Development, Education and Lifelong Learning»

European Commission Research Executive Agency Grant BIORISE

Bioinformatics European Research Area

ERA

European Commission Research Executive Agency

BIORISE

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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