HGM2008 - Poster 12 = - Understanding Wnt cascades through modularization

Poster 12

Understanding Wnt cascades through modularization

Rajat De, Losiana Nayak
Indian = Statistical=20 Institute, 203 Barrackpore Trunk Road, Kolkata 700108, India

Wnts are secreted cysteine-rich, lipid-modified glycoproteins. Wnt = signaling=20 plays crucial role in regulation of cell fate determination, = proliferation,=20 differentiation, migration, body plan formation, chondrocyte = differentiation,=20 limb initiation, bone growth, neural plate formation, and apoptosis. The = pathway=20 diversifies into β-catenin, planar cell polarity and Wnt/Ca2+ = cascades=20 respectively.

Abnormal expression of Wnt family members result in various skin, = bone and=20 nervous disorders. For example, loss of LRP5 function causes OPPG = syndrome while=20 a gain-of-function mutation is reported for the HBM trait. Missense = mutations in=20 LRP5 gene lead to Van Buchem disease, autosomal dominant sclerosteosis = and=20 Osteoporosis type I syndrome. So analysis of Wnt cascades is necessary. = But it=20 is difficult to study these cascades as a whole due to its high degree = of=20 interconnectivity.

Hence we try to divide the human Wnt cascades using a modularization=20 algorithm already developed by the authors, and study the different = modules from=20 biological perspective. Modularization is a process of splitting a = network into=20 sub-networks. Here human Wnt signaling pathway is subjected to be = modularized=20 into simple entities known as modules. A module can be defined as a = subset of=20 the original network that tends to be self-sufficient and has minimal = dependency=20 on the rest part of the network. The algorithm takes care of the fact = that the=20 created modules try to signify one or a distinct part of one function of = the=20 pathway. The input data is taken from KEGG/Pathway database.

The human Wnt signaling pathway gets modularized into 8 modules. The=20 canonical Wnt pathway gets divided into modules WNT16, (DVL1)1, AXIN1, = CTNNB1=20 and LEF1. Module WNT16 includes the Wnt ligand-receptor interactions in = presence=20 of co-receptors, several inhibitors and add-ons. Modules (DVL1)1, AXIN1 = and=20 CTNNB1 encounter for the steps of β-catenin balance and its entry = into nucleus.=20 Module LEF1 counters for further downstream actions that happen inside = nucleus=20 and effect expression levels of many concerned genes. Module (DVL1)2 is = made up=20 of the Planar cell polarity pathway and module PLCB1 is comprised of the = Wnt/Ca2+ pathway. We cannot associate any biological significance to the = very=20 small Tp53 module. Further biological investigations of biomolecules = present in=20 these modules may throw light on cure of the diseases they cause. = Modularized=20 study of Wnt cascades of other species is also done to get an evo devo = view.=20

HGM2008 Poster=20 Abstracts1. Bioinformatics and Statistical Genomics

Poster 12

Understanding Wnt cascades through modularization

HGM2008 Poster=20 Abstracts
1. Bioinformatics and Statistical Genomics