title: A reproducible approach to high-throughput biological data acquisition and integration.
abstract: Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NFκB signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ-free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa.
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Börnigen
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Yo Sup
authors.initials: YS
authors.lastname: Moon
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Gholamali
authors.initials: G
authors.lastname: Rahnavard
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|City University of New York School of Public Health, Hunter College, New York, NY, USA.
authors.forename: Levi
authors.initials: L
authors.lastname: Waldron
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: McIver
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Afrah
authors.initials: A
authors.lastname: Shafquat
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Franzosa
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Miropolsky
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sweeney
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Xochitl C
authors.initials: XC
authors.lastname: Morgan
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Garrett
authors.affiliation: Biostatistics Department, Harvard School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
keywords: Data acquisition; Data integration; Heterogeneous data; High-throughput data; Meta-analysis; Reproducibility