State of the field: An informatics-based systematic review of the SOD1-G93A amyotrophic lateral sclerosis transgenic mouse model

Amyotroph Lateral Scler Frontotemporal Degener. 2015;17(1-2):1-14. doi: 10.3109/21678421.2015.1047455. Epub 2015 May 22.

Abstract

Numerous sub-cellular through system-level disturbances have been identified in over 1300 articles examining the superoxide dismutase-1 guanine 93 to alanine (SOD1-G93A) transgenic mouse amyotrophic lateral sclerosis (ALS) pathophysiology. Manual assessment of such a broad literature base is daunting. We performed a comprehensive informatics-based systematic review or 'field analysis' to agnostically compute and map the current state of the field. Text mining of recaptured articles was used to quantify published data topic breadth and frequency. We constructed a nine-category pathophysiological function-based ontology to systematically organize and quantify the field's primary data. Results demonstrated that the distribution of primary research belonging to each category is: systemic measures an motor function, 59%; inflammation, 46%; cellular energetics, 37%; proteomics, 31%; neural excitability, 22%; apoptosis, 20%; oxidative stress, 18%; aberrant cellular chemistry, 14%; axonal transport, 10%. We constructed a SOD1-G93A field map that visually illustrates and categorizes the 85% most frequently assessed sub-topics. Finally, we present the literature-cited significance of frequently published terms and uncover thinly investigated areas. In conclusion, most articles individually examine at least two categories, which is indicative of the numerous underlying pathophysiological interrelationships. An essential future path is examination of cross-category pathophysiological interrelationships and their co-correspondence to homeostatic regulation and disease progression.

Keywords: Mitochondria; calcium; excitotoxicity; gliosis; neuropathology; protein aggregation; reactive oxygen species; rotarod.

Publication types

  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / classification
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Axonal Transport
  • Disease Models, Animal*
  • Energy Metabolism
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Inflammation / pathology
  • Inflammation / physiopathology*
  • Mice / genetics*
  • Mice, Transgenic
  • Movement
  • Natural Language Processing
  • Neurons / metabolism*
  • Oxidative Stress
  • Periodicals as Topic / statistics & numerical data
  • Polymorphism, Single Nucleotide / genetics
  • Proteome / metabolism
  • Superoxide Dismutase / genetics*

Substances

  • Genetic Markers
  • Proteome
  • SOD1 G93A protein
  • Superoxide Dismutase