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PLoS One. 2015 Dec 16;10(12):e0143274. doi: 10.1371/journal.pone.0143274. eCollection 2015.

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

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Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia.
Faculty of Information Technology, Monash University, Clayton, VIC, 3800, Australia.
Laboratory for Disease Systems Modeling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Okinawa Institute of Science and Technology, Onna, Onna-son, Kunigami, Okinawa, Japan.
National Heart and Lung Institute, Imperial College London, White City, W12 0NN, United Kingdom.
The Jackson Laboratory, Bar Harbor, ME, 04609, United States of America.


The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (, an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

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