Mathematical approaches to investigate diversity of myofibroblast in Dupuytren’s disease

Dupuytren’s disease (DD) is an ill-defined commonly occurring fibroproliferative disorder affecting the palms of the hands. The disease is prevalent in individuals of Northern European Caucasian origin. DD tissues can be classified into
several stages according to their cellularity; the nodule and the cord. The nodule is described as a highly vascularized tissue containing a large number of fibroblasts, with a high percentage being myofibroblasts, as recognized by their
expression of α-smooth muscle actin. The cord however, is relatively avascular and acellular, collagen-rich with few myofibroblasts. There are different opinions regarding the origin and development of this aspect of the DD phenotype,
either viewing the nodule as developing into the cord as the disease progresses over time or, the two structures as representing independent stages of the disease. We designed and performed a study in which the nodule and the cord were considered as two separate entities, as if arisen from separate precursor cells. Gene-expression profiles were compared between diseased Dupuytren’s tissue biopsies (nodules and cords) and corresponding healthy tissue (the transverse palmar fascia adjacent to the diseased site) from the same patients. We also compared these gene-expression profiles with those from the carpal ligamentous fascia from healthy individuals not affected with DD. We adopt a systems biology approach to investigate DD and propose a new method for analyzing gene expression dataset that reduces the number of false positives compared to traditional techniques. Our method leverages the massive amount of publicly available gene expression datasets to establish robust logical relationships between genes and compare it to the differentially expressed genes in DD samples. We develop mathematical models based on the logical relationships. The combination of logical analysis and pathway oriented approach highlights key molecules that are suggestive that DD may arise from innate inflammation related to autoimmunity but may be also be co-activated by
other factors e.g. trauma, mechanical stress, other external/internal factors etc.