Limits...
Scope and limitations of yeast as a model organism for studying human tissue-specific pathways.

Mohammadi S, Saberidokht B, Subramaniam S, Grama A - BMC Syst Biol (2015)

Bottom Line: 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.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.Consequently, they provide excellent candidates as drug targets for therapeutic interventions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Sciences, Purdue University, West Lafayette, 47907, USA. mohammadi@purdue.edu.

ABSTRACT

Background: Budding yeast, S. cerevisiae, has been used extensively as a model organism for studying cellular processes in evolutionarily distant species, including humans. However, different human tissues, while inheriting a similar genetic code, exhibit distinct anatomical and physiological properties. 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.

Results: We present a novel framework to systematically quantify the suitability of yeast as a model organism for different human tissues. To this end, we develop a computational method for dissecting the global human interactome into tissue-specific cellular networks. 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. 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. We further study each of these subspaces in detail, and shed light on their unique biological roles in the human tissues.

Conclusions: 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. 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. 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. Consequently, they provide excellent candidates as drug targets for therapeutic interventions.

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Related in: MedlinePlus

Summary of gene classifications in this study. Housekeeping and tissue-selective genes, in four main groups of human tissues, are classified into three main classes based on their conservation in yeast
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Fig7: Summary of gene classifications in this study. Housekeeping and tissue-selective genes, in four main groups of human tissues, are classified into three main classes based on their conservation in yeast

Mentions: Table 3 presents the number of expressed genes, selectively expressed genes, and the percent of tissue-selective genes that are conserved, human-specific, or unclassified within each group of tissues. There is a similar relationship between the ratio of conserved/human-specific genes within each group of tissues and their alignment p-values, suggesting that alignment p-values are highly correlated with the conservation of tissue-selective genes and their corresponding pathways. Figure 7 illustrates the relative sizes of each subset of genes identified in this study.Fig. 7


Scope and limitations of yeast as a model organism for studying human tissue-specific pathways.

Mohammadi S, Saberidokht B, Subramaniam S, Grama A - BMC Syst Biol (2015)

Summary of gene classifications in this study. Housekeeping and tissue-selective genes, in four main groups of human tissues, are classified into three main classes based on their conservation in yeast
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4696342&req=5

Fig7: Summary of gene classifications in this study. Housekeeping and tissue-selective genes, in four main groups of human tissues, are classified into three main classes based on their conservation in yeast
Mentions: Table 3 presents the number of expressed genes, selectively expressed genes, and the percent of tissue-selective genes that are conserved, human-specific, or unclassified within each group of tissues. There is a similar relationship between the ratio of conserved/human-specific genes within each group of tissues and their alignment p-values, suggesting that alignment p-values are highly correlated with the conservation of tissue-selective genes and their corresponding pathways. Figure 7 illustrates the relative sizes of each subset of genes identified in this study.Fig. 7

Bottom Line: 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.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.Consequently, they provide excellent candidates as drug targets for therapeutic interventions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Sciences, Purdue University, West Lafayette, 47907, USA. mohammadi@purdue.edu.

ABSTRACT

Background: Budding yeast, S. cerevisiae, has been used extensively as a model organism for studying cellular processes in evolutionarily distant species, including humans. However, different human tissues, while inheriting a similar genetic code, exhibit distinct anatomical and physiological properties. 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.

Results: We present a novel framework to systematically quantify the suitability of yeast as a model organism for different human tissues. To this end, we develop a computational method for dissecting the global human interactome into tissue-specific cellular networks. 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. 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. We further study each of these subspaces in detail, and shed light on their unique biological roles in the human tissues.

Conclusions: 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. 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. 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. Consequently, they provide excellent candidates as drug targets for therapeutic interventions.

Show MeSH
Related in: MedlinePlus