These conserved biochemical pathways drive cellular growth, division, trafficking, stress-response, and secretion, among others, all of which are known to be associated with various human pathologies. In the majority of cases, yeast has been the model organism in which these pathways were originally identified and studied. Yeast and humans share a significant fraction of their functional pathways that control key aspects of eukaryotic cell biology, including the cell cycle, metabolism, programmed cell death, protein folding, quality control and degradation, vesicular transport, and many key signaling pathways, such as mitogen-activated protein kinase (MAPK), target of rapamycin (TOR), and insulin/IGF-I signaling pathways. These methods have been previously applied to detection of ortholog proteins, projection of functional pathways, and construction of phylogenetic trees. Network alignments use both the homology of genes, as well as their underlying interactions, to project functional pathways across different species. Comparative analysis of these pathways relies on network alignment methods, much the same way as sequence matching and alignments are used for individual genes and proteins. These interactions, also referred to as the interactome, embody a complex network of functional pathways that closely work together to modulate the cellular machinery. With the advent of “systems modeling”, a diverse set of methods have been devised to assay the interactions, both physical and functional, among different active entities in the cell, including protein-protein, protein-DNA, and genetic interactions. These -omic datasets, all originally developed in yeast, aim to capture dynamic snapshots of the state of biomolecules during cellular activities. The maturity of yeast’s genetic and molecular toolbox has, in turn, positioned it as the primary platform for development of many high-throughput technologies, including transcriptome, proteome, and metabolome screens. Motivated by the availability of its full genome in 1996 as the first eukaryotic organism to be sequenced, an array of functional genomics tools emerged, including a comprehensive collection of yeast deletion mutants, genome-wide over-expression libraries, and green fluorescent protein (GFP)-tagged yeast strains. Coupled with the continuous development of new experimental methodologies for manipulating various aspects of its cellular machinery, it has served as the primary model organism for molecular and systems biology. cerevisiae, is widely used as an experimental system, due to its ease of manipulation in both haploid and diploid forms, and rapid growth compared to animal models. Consequently, they provide excellent candidates as drug targets for therapeutic interventions.īudding yeast, S. While tissue-selective genes are significantly associated with the onset and development of a number of tissue-specific pathologies, we show that the human-specific subset has even higher association. Many complex disorders are driven by a coupling of housekeeping (universally expressed in all tissues) and tissue-selective (expressed only in specific tissues) dysregulated pathways. Our framework provides a novel tool that can be used to assess the suitability of the yeast model for studying tissue-specific physiology and pathophysiology in humans. We further study each of these subspaces in detail, and shed light on their unique biological roles in the human tissues. Finally, we couple our framework with a novel statistical model to assess the conservation of tissue-specific pathways and infer the overall similarity of each tissue with yeast. By individually aligning these networks with the yeast interactome, we simultaneously partition the functional space of human genes, and their corresponding pathways, based on their conservation both across species and among different tissues. To this end, we develop a computational method for dissecting the global human interactome into tissue-specific cellular networks. We present a novel framework to systematically quantify the suitability of yeast as a model organism for different human tissues. Specific biochemical processes and associated biomolecules that differentiate various tissues are not completely understood, neither is the extent to which a unicellular organism, such as yeast, can be used to model these processes within each tissue. However, different human tissues, while inheriting a similar genetic code, exhibit distinct anatomical and physiological properties. cerevisiae, has been used extensively as a model organism for studying cellular processes in evolutionarily distant species, including humans.
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