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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Membership distribution of non-housekeeping genes in human tissues. The number of tissues in which non-housekeeping genes are expressed in is smoothed using Gaussian kernel density. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a few selected tissues or in the majority of human tissues
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Fig5: Membership distribution of non-housekeeping genes in human tissues. The number of tissues in which non-housekeeping genes are expressed in is smoothed using Gaussian kernel density. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a few selected tissues or in the majority of human tissues

Mentions: Figure 5 presents the probability density function for the membership distribution of non-housekeeping genes in different human tissues. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a very few selected tissues or in the majority of human tissues. We use this to partition the set of expressed non-housekeeping genes, with the goal of identifying genes that are selectively expressed in each group of human tissues.Fig. 5


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)

Membership distribution of non-housekeeping genes in human tissues. The number of tissues in which non-housekeeping genes are expressed in is smoothed using Gaussian kernel density. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a few selected tissues or in the majority of human tissues
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Membership distribution of non-housekeeping genes in human tissues. The number of tissues in which non-housekeeping genes are expressed in is smoothed using Gaussian kernel density. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a few selected tissues or in the majority of human tissues
Mentions: Figure 5 presents the probability density function for the membership distribution of non-housekeeping genes in different human tissues. The observed bi-modal distribution suggests that most non-housekeeping genes are either expressed in a very few selected tissues or in the majority of human tissues. We use this to partition the set of expressed non-housekeeping genes, with the goal of identifying genes that are selectively expressed in each group of human tissues.Fig. 5

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