Systems biology of complex symptom profiles: Capturing interactivity across behavior, brain and immune regulation

Abstract

As our thinking about the basic principles of biology and medicine continue to evolve, the importance of context and regulatory interaction is becoming increasingly obvious. Biochemical and physiological components do not exist in isolation but instead are part of a tightly integrated network of interacting elements that ensure robustness and support the emergence of complex behavior. This integration permeates all levels of biology from gene regulation, to immune cell signaling, to coordinated patterns of neuronal activity and the resulting psychosocial interaction. Systems biology is an emerging branch of science that sits as a translational catalyst at the interface of the life and computational sciences. While there is no universally accepted definition of systems biology, we attempt to provide an overview of some the basic unifying concepts and current efforts in the field as they apply to illnesses where brain and subsequent behavior are a chief component, for example autism, schizophrenia, depression, and others. Methods in this field currently constitute a broad mosaic that stretches across multiple scales of biology and physiological compartments. While this work by no means constitutes an exhaustive list of all these methods, this work highlights the principal sub-disciplines presently driving the field as well as future directions of progress.

Age, plasticity, and homeostasis in childhood brain disorders

“…Unbridled stable homeostasis would generate a brain that could respond quickly to existing routines and information, but respond poorly to novelty or insult. Whether plasticity will be adaptive or maladaptive depends on homeostatic regulation, which exists at the level of gene, transcript, protein, metabolite, cell, and brain (Broderick & Craddock, 2012). …”

Epigenomic Mechanisms of Early Adversity and HPA Dysfunction: Considerations for PTSD Research

“…The data will also provide a valuable method to identify epigenetically invariant genomic regions that can serve to reduce genomic complexity in genome-wide analysis of epigenetic signaling, and transcriptional “silent” regions in specified cell types unlikely to be responsive to environmental perturbations. These data, together with an accumulating array of published epigenomic analysis, should help move research on the impacts of early life adversity beyond candidate gene to “candidate pathway” and “candidate network” levels of analysis, which are finding utility in other areas of complex disease research [e.g., (38)].…”

Suicidal Behaviors Among Adolescents in Juvenile Detention: Role of Adverse Life Experiences

“…The data will also provide a valuable method to identify epigenetically invariant genomic regions that can serve to reduce genomic complexity in genomewide analysis of epigenetic signaling, and transcriptional "silent" regions in specified cell types unlikely to be responsive to environmental perturbations. These data, together with an accumulating array of published epigenomic analysis, should help move research on the impacts of early life adversity beyond candidate gene to "candidate pathway" and "candidate network" levels of analysis, which are finding utility in other areas of complex disease research [e.g., (38)]. …”