PUBLICATION

Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species

Authors
Lausser, L., Siegle, L., Rottbauer, W., Frank, D., Just, S., Kestler, H.A.
ID
ZDB-PUB-181130-13
Date
2018
Source
Biomolecules   8(4): (Journal)
Registered Authors
Just, Steffen, Rottbauer, Wolfgang
Keywords
Heart failure phenotypes, Wistar rat, semantic multi-classifier systems, zebrafish
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Gene Ontology
  • Genotype
  • Heart Failure/genetics*
  • Heart Failure/physiopathology
  • Heterozygote
  • Homozygote
  • Humans
  • Metabolic Networks and Pathways/genetics*
  • Mutation
  • Myocardial Contraction/genetics*
  • Myocardial Contraction/physiology
  • Rats
  • Semantics
  • Zebrafish/genetics*
PubMed
30486323 Full text @ Biomolecules
Abstract
Genetic model organisms have the potential of removing blind spots from the underlying gene regulatory networks of human diseases. Allowing analyses under experimental conditions they complement the insights gained from observational data. An inevitable requirement for a successful trans-species transfer is an abstract but precise high-level characterization of experimental findings. In this work, we provide a large-scale analysis of seven weak contractility/heart failure genotypes of the model organism zebrafish which all share a weak contractility phenotype. In supervised classification experiments, we screen for discriminative patterns that distinguish between observable phenotypes (homozygous mutant individuals) as well as wild-type (homozygous wild-types) and carriers (heterozygous individuals). As the method of choice we use semantic multi-classifier systems, a knowledge-based approach which constructs hypotheses from a predefined vocabulary of high-level terms (e.g., Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways or Gene Ontology (GO) terms). Evaluating these models leads to a compact description of the underlying processes and guides the screening for new molecular markers of heart failure. Furthermore, we were able to independently corroborate the identified processes in Wistar rats.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes