Syndromics: A Bioinformatics Approach for Neurotrauma Research

Abstract

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings.

Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury

“…Chronically denervated lumbosacral segments showed sprouting of myelinated primary afferent fibres, increased intraspinal axon density, enhanced bidirectional connectivity between distant spinal segments, and upregulation of the number of glutamatergic synaptic terminals. Using a syndromic analysis (Ferguson et al, 2011(Ferguson et al, , 2013, we established mechanistic relationships between this extensive anatomical reorganization, and the alteration of reflex behaviour and stepping capacities. These results suggested that injury-induced rewiring of denervated spinal segments formed aberrant sensorimotor circuits that caused abnormal reflex responses and recruited inappropriate combinations of neuronal networks during gait execution.…”

Personalized Neuroprosthetics

“…Data-mining techniques provide statistical tools to articulate this classification with objective markers gathered into multicenter database, to create evidence-based personalization of treatment design (92). For example, the Stanford, Harvard, and University of California, Los Angeles, hospitals are among the first to digitize patient records, allowing "Google search" across a patients' health history.…”

Derivation of Multivariate Syndromic Outcome Metrics for Consistent Testing across Multiple Models of Cervical Spinal Cord Injury in Rats

“…Here, we provide a novel approach to measure the ‘syndromic space’ [18], [19] from heterogeneous outcome scales in preclinical models of neurological disorders, using SCI as an illustrating example. We first built an information-rich database containing the total set of detailed behavioral and histological outcomes from 159 rats with various types of experimental cervical SCI and multiple outcome metrics (>15,000 data points).…”