From word models to executable models of signaling networks using automated assembly

Mol Syst Biol. 2017 Nov 24;13(11):954. doi: 10.15252/msb.20177651.


Word models (natural language descriptions of molecular mechanisms) are a common currency in spoken and written communication in biomedicine but are of limited use in predicting the behavior of complex biological networks. We present an approach to building computational models directly from natural language using automated assembly. Molecular mechanisms described in simple English are read by natural language processing algorithms, converted into an intermediate representation, and assembled into executable or network models. We have implemented this approach in the Integrated Network and Dynamical Reasoning Assembler (INDRA), which draws on existing natural language processing systems as well as pathway information in Pathway Commons and other online resources. We demonstrate the use of INDRA and natural language to model three biological processes of increasing scope: (i) p53 dynamics in response to DNA damage, (ii) adaptive drug resistance in BRAF-V600E-mutant melanomas, and (iii) the RAS signaling pathway. The use of natural language makes the task of developing a model more efficient and it increases model transparency, thereby promoting collaboration with the broader biology community.

Keywords: computational modeling; natural language processing; signaling pathways.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Computer Simulation
  • DNA Damage
  • Drug Resistance, Neoplasm / genetics
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Indoles / therapeutic use
  • Language
  • Melanoma / drug therapy
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Models, Genetic*
  • Natural Language Processing*
  • Neural Networks, Computer*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Signal Transduction
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Sulfonamides / therapeutic use
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Vemurafenib


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Indoles
  • Sulfonamides
  • Tumor Suppressor Protein p53
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)