Abstract

Abstract The Berg Interrogative Biology™ Informatics Suite is an automated data-processing instrument for generation of actionable hypotheses using data generated exclusively via the Berg Interrogative Biology™ approach. The Berg Interrogative Biology™ is a platform that systematically interrogates the biological environment in proprietary in-vitro and in-vivo biological model systems. The biologically relevant data output include molecular data from multi-omics technologies such as proteomics, lipidomics, metabolomics and genomics generated within the context of Berg Interrogative Biology™ is subsequently processed by a set of mathematical algorithms within Informatics Suite. The steps include filtering of datasets with methods that allows for missing data without compromising data quality, normalization of data using technology specific methods, imputation of missing data by rigorous statistical approaches, and generation of a molecular interactome model by integrating data across experiments and technologies. Consequently, the multi-omics data is subjected to analysis using a Bayesian Network inference approach and a multi-omic cause-and-effect relationships are inferred for each analyzed condition de novo. In addition to inferring cross-molecular species interaction networks, in-silico perturbation experiments may be performed to predict cascades of molecular and phenotypic responses to a gene or protein knock-down or over-expression model. Model response is analyzed by statistical techniques and submitted to a Rich Internet Application (RIA) that allows a dynamic and interactive meta-analysis of integrated molecular interaction networks. The Informatics Suite pipeline was applied to multi-omic data set generated via the use of the Berg Interrogative Biology™ process in an in-vitro model of angiogenesis. Comprehensive implementation of the platform technology with the informatics workflow not only identified new and physiologically relevant molecular interactions, but also confirmed previously known canonical interaction pathways described in the literature. Thus, the Informatics Suite within the Berg Interrogative Biology™ platform represents a novel computational component for integrative analysis of multi-omics molecular data that is fast, accurate and leads to a rank-ordered number of actionable hypotheses positioning Berg Interrogative Biology™ as one of the most innovative and efficient approaches in drug and biomarker discovery. Citation Format: Leonardo Rodrigues, Vijetha Vemulapalli, Anthony Walshe, Min Du, Michael Keibish, Joaquin J. Jimenez, Vivek K. Vishnudas, Rangaprasad Sarangarajan, Viatcheslav R. Akmaev, Niven R. Narain. Berg Interrogative Biology™ Informatics Suite: data driven integration of multi-omic technologies using Bayesian AI. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5230. doi:10.1158/1538-7445.AM2013-5230

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