Abstract
A large and growing body of research implicates aberrant immune response and compositional shifts of the intestinal microbiota in the pathogenesis of many intestinal disorders. The molecular and physical interaction between the host and the microbiota, known as the host-microbiota interactome, is one of the key drivers in the pathophysiology of many of these disorders. This host-microbiota interactome is a set of dynamic and complex processes, and needs to be treated as a distinct entity and subject for study. Disentangling this complex web of interactions will require novel approaches, using a combination of data-driven bioinformatics with knowledge-driven computational modeling. This review describes the computational approaches for investigating the host-microbiota interactome, with emphasis on the human intestinal tract and innate immunity, and highlights open challenges and existing gaps in the computation methodology for advancing our knowledge about this important facet of human health.
Highlights
The Human Microbiome Project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT)are two large-scale data collection projects that have helped to spur research on the microbial communitiesComputation 2015, 3 that inhibit various niches of the human body [1,2,3]
The primary hypothesis of the pathogenesis of these intestinal disorders invokes a series of stages in the progression from a healthy state to disease, whereby external perturbations, genetic predispositions and host-microbiota feedback interactions lead to a self-sustaining chronic state involving host dysfunction and microbiota dysbiosis
The host-microbiota interactome is the frontier in the nascent field of translational systems biology and bioinformatics
Summary
The Human Microbiome Project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT). Along the disease trajectory the commensal microbiota may enter a dysbiotic state by shifting towards a pathobiome, which further enforces a pathogenic host response [17] It is this interactome that is the current “black box” of the intestinal system: peering into and manipulating this black box holds the promise of designing interventions that can control the interaction dynamics and guide the system towards a healthy outcome (Figure 1). Computational models are abstractions of the real biological system and require experimental data to validate and calibrate their behavior, and they produce simulated data that looks much like experimental data, which requires bioinformatics to properly analyze This review covers both methodologies in the study of the host-microbiota interactome and highlights efforts to combine the two approaches. Instead we will highlight the current open challenges in the field and existing gaps in the integration of multiple techniques, with the hope that it will encourage research in new computational methods
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