Cancer hybrid automata: Model, beliefs and therapy

Loes Olde Loohuis, Andreas Witzel, Bhubaneswar Mishra

Research output: Contribution to journalArticle

Abstract

This paper introduces Cancer Hybrid Automata (CHAs), a formalism to model the progression of cancers through discrete phenotypes. The classification of cancer progression using discrete states like stages and hallmarks has become common in the biology literature, but primarily as an organizing principle, and not as an executable formalism. The precise computational model developed here aims to exploit this untapped potential, namely, through automatic verification of progression models (e.g., consistency, causal connections, etc.), classification of unreachable or unstable states and computer-generated (individualized or universal) therapy plans. The paper builds on a phenomenological approach, and as such does not need to assume a model for the biochemistry of the underlying natural progression. Rather, it abstractly models transition timings between states as well as the effects of drugs and clinical tests, and thus allows formalization of temporal statements about the progression as well as notions of timed therapies. The model proposed here is ultimately based on hybrid automata, and we show how existing controller synthesis algorithms can be generalized to CHA models, so that therapies can be generated automatically. Throughout this paper we use cancer hallmarks to represent the discrete states through which cancer progresses, but other notions of discretely or continuously varying state formalisms could also be used to derive similar therapies.

Original languageEnglish (US)
Pages (from-to)68-86
Number of pages19
JournalInformation and Computation
Volume236
DOIs
StatePublished - 2014

Fingerprint

Hybrid Automata
Therapy
Cancer
Progression
Model
Automatic Verification
Transition Model
Biochemistry
Formalization
Phenotype
Computational Model
Biology
Beliefs
Timing
Drugs
Unstable
Synthesis
Controller
Controllers

Keywords

  • Automatic therapy design
  • Belief
  • Cancer progression
  • Controller synthesis
  • Hybrid automata
  • Tests

ASJC Scopus subject areas

  • Information Systems
  • Computational Theory and Mathematics
  • Theoretical Computer Science
  • Computer Science Applications

Cite this

Cancer hybrid automata : Model, beliefs and therapy. / Olde Loohuis, Loes; Witzel, Andreas; Mishra, Bhubaneswar.

In: Information and Computation, Vol. 236, 2014, p. 68-86.

Research output: Contribution to journalArticle

Olde Loohuis, Loes ; Witzel, Andreas ; Mishra, Bhubaneswar. / Cancer hybrid automata : Model, beliefs and therapy. In: Information and Computation. 2014 ; Vol. 236. pp. 68-86.
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