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Updated: Oct 7, 2025

Discrimination and Characterization of Heterocellular Populations Using Quantitative Imaging Techniques
Published on: June 30, 2017
The differential activity of biological processes in tissues and cell subsets can illuminate disease-related
Moran Sharon1, Ekaterina Vinogradov1, Chanan M Argov1
1Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Motivation:
The distinct functionalities of human tissues and cell types underlie complex phenotype-genotype relationships, yet often remain elusive. Harnessing the multitude of bulk and single-cell human transcriptomes while focusing on processes can help reveal these distinct functionalities.
Results:
The Tissue-Process Activity (TiPA) method aims to identify processes that are preferentially active or under-expressed in specific contexts, by comparing the expression levels of process genes between contexts. We tested TiPA on 1579 tissue-specific processes and bulk tissue transcriptomes, finding that it performed better than another method. Next, we used TiPA to ask whether the activity of certain processes could underlie the tissue-specific manifestation of 1233 hereditary diseases. We found that 21% of the disease-causing genes indeed participated in such processes, thereby illuminating their genotype-phenotype relationships. Lastly, we applied TiPA to single-cell transcriptomes of 108 human cell types, revealing that process activities often match cell-type identities and can thus aid annotation efforts. Hence, differential activity of processes can highlight the distinct functionality of tissues and cells in a robust and meaningful manner.
Availability And Implementation:
TiPA code is available in GitHub (https://github.com/moranshar/TiPA). In addition, all data are available as part of the Supplementary Material.
Supplementary Information:
Supplementary data are available at Bioinformatics online.

