July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Lens-PaTrNing: an interactive web resource for interrogating signal Pathways and Transcriptional Networking during lens and cataract formation
Author Affiliations & Notes
  • Michael O'Connor
    Western Sydney University, Penrith, New South Wales, Australia
  • James Monks
    Western Sydney University, Penrith, New South Wales, Australia
  • Md. Humayun Kabir
    Western Sydney University, Penrith, New South Wales, Australia
  • Joshua Wing Kei Ho
    The University of Hong Kong, Hong Kong
  • Liwan Liyanage
    Western Sydney University, Penrith, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Michael O'Connor, None; James Monks, None; Md. Humayun Kabir, None; Joshua Ho, None; Liwan Liyanage, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3433. doi:https://doi.org/
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      Michael O'Connor, James Monks, Md. Humayun Kabir, Joshua Wing Kei Ho, Liwan Liyanage; Lens-PaTrNing: an interactive web resource for interrogating signal Pathways and Transcriptional Networking during lens and cataract formation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3433. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Defining the complex integration of signal pathways during tissue development and disease is a key frontier in systems biology. We have created a new web resource using public proteomic and transcriptomic data to predict novel molecular hypotheses of lens and cataract development.

Methods : Public human and mouse lens gene expression datasets from various ages were combined with multi-species protein interaction data and cataract-associated genes using R. Commonly-expressed and lens-enriched genes were identified using compendium-based analyses. The data was combined into a web-based platform.

Results : Lens-PaTrNing enables visualization of receptors, kinases and transcriptional regulators expressed by lens epithelial and fiber cells. This includes over 250 growth factor, cell-cell and cell-matrix signaling pathways. Correlation of these signaling pathways with target gene predictions allows extracellular-mediated control of lens gene expression to be investigated. The pathway/target gene data can be accessed: as receptor-defined pathways; by kinases and/or transcriptional regulators that are unique to individual pathways or common to multiple pathways; or by searching for individual genes to identify associated regulatory pathways. Each pathway contains interactive nodes that link to external resources. Side-by-side comparison of multiple pathways is possible, as is overlay of known cataract-associated genes on signal pathways and predicted target genes. This unique combination of interactive tools enables non-bioinformaticists to rapidly visualize lens signaling pathways and their involvement with known cataract-associated genes. Investigation of these signal pathway/target gene predictions identified over 100 pathways that regulate at least 50 cataract-associated genes, including critically-required lens pathways (e.g., Fgf), transcription factors (e.g., Pax6) and known cataract-associated genes (e.g., crystallins).

Conclusions : The Lens-PaTrNing web interface is a powerful new public tool that enables non-bioinformaticians to visualize extrinsic and intrinsic lens signal pathways, their interconnections, and associated predicted target genes. In this way Lens-PaTrNing facilitates simple generation of candidate molecular mechanisms that can form the basis for hypothesis creation and hypothesis-driven investigation of lens and cataract formation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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