An Interactive Pathway Map in Excel

Introduction

The adult mammalian heart contains many different cell types that work in unison under tightly regulated conditions to maintain homeostasis. The cardiac fibroblast (CFb) originates from several sources, especially the mesenchymal stem cell [1]. This under-appreciated cell type may account for 50-70% of heart composition [2] and their systems-level functions are still largely unexplored. Our group recently reported that the adult CFb expresses a number of cardiogenic genes [3], underscoring the needs to better understand this cell type.

We collected ~1400 articles from the NCBI PubMed database that mentioned the cardiac fibroblasts in their text. First, we performed algorithm-based text mining using standard tools: BioIE, Whatizit, and MEDIE. However, algorithm-based approaches might yield considerable errors in the predicted biological entities and relationships. For well-studied areas, the errors could be reconciled by comparing different sources describing the same relationship. In the context of mapping the cardiac fibroblast network from a relatively sparse body of literature, the classification errors are especially detrimental as any mislabelling will prevent further analysis of the cardiac fibroblast pathway.

From the collected literature data, we built an interactive cardiac fibroblasts pathway map (CARFMAP) implemented as biologist-centric software with intuitive user interface (see below figure). CARFMAP employs a polar layout such that it mimics the spatial distribution of the cellular components. Drugs (red), extracellular proteins (grey), and extracellular phenotypes (orange) are placed at the outer rings. The next ring contains membrane receptors (green). Next to this ring are several rings of intracellular proteins (grey), followed by gene expressions (cyan) and finally phenotypes (yellow). Network overlap algorithm detected the common pathways between CARFMAP and a foreskin fibroblasts pathway map.

Subnetworks of CARFMAP

Subnetworks of CARFMAP

DEMO Video

Below is a photo of CARFMAP being deployed on a high-resolution 12K monitor wall at Monash University's sensiLab. A brief demostration video of CARFMAP function can be viewed by clicking the below image ("Right click \ Save Link As" to download).

CARFMAP on a 6-monitor display wall

To get started

The CARFMAP can be downloaded as a zip package here. As CARFMAP was built for the Microsoft Excel platform, it requires a Windows 7 or above machine with Excel installed. See README.txt inside the zip package for installation instructions.

The R script for the bioinformatics analysis pipeline described in the CARFMAP manuscript is available here.

References:

1. Souders, C.A., Bowers, S.L. and Baudino, T.A. (2009) Cardiac fibroblast: the renaissance cell, Circulation research, 105, 1164-1176.

2. Turner, N.A. (2011) The Cardiac Fibroblast. Research Signpost.

3. Furtado MB, Costa MW, Pranoto EA, Salimova E, Pinto AR, et al. (2014) Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair. Circulation research 114: 1422-1434.

 

Monash University         SBI Australia