RT Journal Article
SR Electronic
T1 Unsupervised logic-based mechanism inference for network-driven biological processes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.15.422874
DO 10.1101/2020.12.15.422874
A1 Martina Prugger
A1 Lukas Einkemmer
A1 Samantha P. Beik
A1 Leonard A. Harris
A1 Carlos F. Lopez
YR 2020
UL http://biorxiv.org/content/early/2020/12/15/2020.12.15.422874.abstract
AB Modern analytical techniques enable researchers to collect data about cellular states, before and after perturbations. These states can be characterized using analytical techniques, but the inference of regulatory interactions that explain and predict changes in these states remains a challenge. Here we present a generalizable unsupervised approach to generate parameter-free, logic-based mechanistic hypotheses of cellular processes, described by multiple discrete states. Our algorithm employs a Hamming-distance based approach to formulate, test, and identify, the best mechanism that links two states. Our approach comprises two steps. First, a model with no prior knowledge except for the mapping between initial and attractor states is built. Second, we employ biological constraints to improve model fidelity. Our algorithm automatically recovers the relevant dynamics for the explored models and recapitulates all aspects of the original models biochemical species concentration dynamics. We then conclude by placing our results in the context of ongoing work in the field and discuss how our approach could be used to infer mechanisms of signaling, gene-regulatory, and any other input-output processes describable by logic-based mechanisms.