Tissue-Tissue Similarity Network (TTSN):
A New Perspective on the Tissue-Selectivity of the Human Transcriptome

Shahin Mohammadi and Ananth Grama

Identification of biochemical processes that drive the transformation of a totipotent cell into various cell types is essential to our understanding of living systems. This complex machinery determines how tissues differ in terms of their anatomy, physiology, morphology, and, more importantly, how various cellular control mechanisms contribute to the observed similarities/ differences. Tissue-selective genes orchestrate various aspects of cellular machinery in different tissues, and are known to be implicated in a number of tissue-specific pathologies.

We propose a novel statistical approach for constructing a network of tissue-tissue similarities. We utilize this network as a refined prior for a new method aimed at identification of tissue-selective functions and their corresponding genes. Using a case study of brain tissues, we show that our approach significantly outperforms state-of-the-art methods, both in terms of coverage and reliability of predicted tissue-selective genes, as well as their significance in characterizing pathophysiology of human tissues.

Our results include a first-of-its-kind network of tissue-tissue similarity that provides a means for projecting prior knowledge of tissue-specific functions across the set of related tissues. These results also include highly reliable brain-selective functions and proteins, as well as a general framework that can be extended to construct similar datasets in other human tissues. These tissue-selective targets greatly enhance our understanding of differentiating biochemical features of brain tissues, shed light on how brain-selective pathologies progress, and help us identify specific biomarkers and targets for future interventions.

Keywords: Tissue-selectivity, Tissue-specificity, Tissue-tissue similarity network, GNF Gene Atlas

Supplementary Materials
News & Announcements
2013-10-22 14:31:06
Paper was Submitted to RECOMB 2014

2013-07-31 10:53:45
Project "Tissue-Tissue Similarity Network (TTSN): A New Window to the Tissue-Selectivity of Human Proteins" was created.