Dataset Information

Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks.

ABSTRACT:

Background

Messenger RNA expression is regulated by a complex interplay of different regulatory proteins. Unfortunately, directly measuring the individual activity of these regulatory proteins is difficult, leaving us with only the resulting gene expression pattern as a marker for the underlying regulatory network or regulator-gene associations. Furthermore, traditional methods to predict these regulator-gene associations do not define the relative importance of each association, leading to a large number of connections in the global regulatory network that, although true, are not useful.

Results

Here we present a Bayesian method that identifies which known transcriptional relationships in a regulatory network are consistent with a given body of static gene expression data by eliminating the non-relevant ones. The Partially Observed Bipartite Network (POBN) approach developed here is tested using E. coli expression data and a transcriptional regulatory network derived from RegulonDB. When the regulatory network for E. coli was integrated with 266 E. coli gene chip observations, POBN identified 93 out of 570 connections that were either inconsistent or not adequately supported by the expression data.

Conclusion

POBN provides a systematic way to integrate known transcriptional networks with observed gene expression data to better identify which transcriptional pathways are likely responsible for the observed gene expression pattern.

SUBMITTER: Alvarez A

PROVIDER: S-EPMC3117734 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks.

Alvarez Angel A Woolf Peter J PJ

BMC systems biology 20110527

<h4>Background</h4>Messenger RNA expression is regulated by a complex interplay of different regulatory proteins. Unfortunately, directly measuring the individual activity of these regulatory proteins is difficult, leaving us with only the resulting gene expression pattern as a marker for the underlying regulatory network or regulator-gene associations. Furthermore, traditional methods to predict these regulator-gene associations do not define the relative importance of each association, leading ...[more]

PMID: 21619639

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Project description:BACKGROUND:This is a case study from an HIV prevention project among young black men who have sex with men. Individual-level prevention interventions have had limited success among young black men who have sex with men, a population that is disproportionately affected by HIV; peer network-based interventions are a promising alternative. Facebook is an attractive digital platform because it enables broad characterization of social networks. There are, however, several challenges in using Facebook data for peer interventions, including the large size of Facebook networks, difficulty in assessing appropriate methods to identify candidate peer change agents, boundary specification issues, and partial observation of social network data. OBJECTIVE:This study aimed to explore methodological challenges in using social Facebook networks to design peer network-based interventions for HIV prevention and present techniques to overcome these challenges. METHODS:Our sample included 298 uConnect study respondents who answered a bio-behavioral survey in person and whose Facebook friend lists were downloaded (2013-2014). The study participants had over 180,000 total Facebook friends who were not involved in the study (nonrespondents). We did not observe friendships between these nonrespondents. Given the large number of nonrespondents whose networks were partially observed, a relational boundary was specified to select nonrespondents who were well connected to the study respondents and who may be more likely to influence the health behaviors of young black men who have sex with men. A stochastic model-based imputation technique, derived from the exponential random graph models, was applied to simulate 100 networks where unobserved friendships between nonrespondents were imputed. To identify peer change agents, the eigenvector centrality and keyplayer positive algorithms were used; both algorithms are suitable for identifying individuals in key network positions for information diffusion. For both algorithms, we assessed the sensitivity of identified peer change agents to the imputation model, the stability of identified peer change agents across the imputed networks, and the effect of the boundary specification on the identification of peer change agents. RESULTS:All respondents and 78.9% (183/232) of nonrespondents selected as peer change agents by eigenvector on the imputed networks were also selected as peer change agents on the observed networks. For keyplayer, the agreement was much lower; 42.7% (47/110) and 35.3% (110/312) of respondent and nonrespondent peer change agents, respectively, selected on the imputed networks were also selected on the observed network. Eigenvector also produced a stable set of peer change agents across the 100 imputed networks and was much less sensitive to the specified relational boundary. CONCLUSIONS:Although we do not have a gold standard indicating which algorithm produces the most optimal set of peer change agents, the lower sensitivity of eigenvector centrality to key assumptions leads us to conclude that it may be preferable. The methods we employed to address the challenges in using Facebook networks may prove timely, given the rapidly increasing interest in using online social networks to improve population health.

Dataset Information

Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks.

Background

Results

Conclusion

Publications

Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks.

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