DEPCs (Crespo et al. 2013)
Crespo I, Perumal TM, Jurkowski W, del Sol A
2013 · BMC systems biology
BACKGROUND: Cellular differentiation and reprogramming are processes that are carefully orchestrated by the activation and repression of specific sets of genes.
Abstract
From the original paper, BMC systems biology · PubMed
BACKGROUND: Cellular differentiation and reprogramming are processes that are carefully orchestrated by the activation and repression of specific sets of genes. An increasing amount of experimental results show that despite the large number of genes participating in transcriptional programs of cellular phenotypes, only few key genes, which are coined here as reprogramming determinants, are required to be directly perturbed in order to induce cellular reprogramming. However, identification of reprogramming determinants still remains a combinatorial problem, and the state-of-art methods addressing this issue rests on exhaustive experimentation or prior knowledge to narrow down the list of candidates. RESULTS: Here we present a computational method, without any preliminary selection of candidate genes, to identify reduced subsets of genes, which when perturbed can induce transitions between cellular phenotypes. The method relies on the expression profiles of two stable cellular phenotypes along with a topological analysis stability elements in the gene regulatory network that are necessary to cause this multi-stability. Since stable cellular phenotypes can be considered as attractors of gene regulatory networks, cell fate and cellular reprogramming involves transition between these attractors, and therefore current method searches for combinations of genes that are able to destabilize a specific initial attractor and stabilize the final one in response to the appropriate perturbations. CONCLUSIONS: The method presented here represents a useful framework to assist researchers in the field of cellular reprogramming to design experimental strategies with potential applications in the regenerative medicine and disease modelling.
Summary
Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how DEPCs (Crespo et al. 2013) relates to the cross-modality inverse-design framework of the review.
Why this level
Level 3 because candidate interventions enter an explicit forward operator and the predicted post-intervention outcome is what scores each candidate. Representation family is executable intervention model. Cited in §3.4 of the review. Editorial rationale pending review by the maintainer.