Date of Original Version

7-2013

Type

Article

Journal Title

Bioinformatics

Volume

29

Issue

13

First Page

i217

Last Page

i226

Rights Management

Copyright The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract or Description

MOTIVATION:

An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of host-pathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called 'multitask learning', which considers the problem of building models across tasks that are related to each other. A 'task' in our scenario is the set of host-pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks.

RESULTS:

Our current work on host-pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a task-based regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex-Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host-pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights.

AVAILABILITY:

The predictions and code are available at: http://www.cs.cmu.edu/∼mkshirsa/ismb2013_paper320.html .

DOI

10.1093/bioinformatics/btt245

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Published In

Bioinformatics, 29, 13, i217-i226.