Systematic analysis of complex genetic interactions

Elena Kuzmin; Benjamin VanderSluis; Wen Wang; Guihong Tan; Raamesh Deshpande; Yiqun Chen; Matej Usaj; Attila Balint; Mojca Mattiazzi Usaj; Jolanda Van Leeuwen; Elizabeth N. Koch; Carles Pons; Andrius J. Dagilis; Michael Pryszlak; Jason Zi Yang Wang; Julia Hanchard; Margot Riggi; Kaicong Xu; Hamed Heydari; Bryan Joseph San Luis; Ermira Shuteriqi; Hongwei Zhu; Nydia Van Dyk; Sara Sharifpoor; Michael Costanzo; Robbie Loewith; Amy Caudy; Daniel Bolnick; Grant W. Brown; Brenda J. Andrews; Charles Boone; Chad L. Myers

doi:10.1126/science.aao1729

Systematic analysis of complex genetic interactions

Elena Kuzmin, Benjamin VanderSluis, Wen Wang, Guihong Tan, Raamesh Deshpande, Yiqun Chen, Matej Usaj, Attila Balint, Mojca Mattiazzi Usaj, Jolanda Van Leeuwen, Elizabeth N. Koch, Carles Pons, Andrius J. Dagilis, Michael Pryszlak, Jason Zi Yang Wang, Julia Hanchard, Margot Riggi, Kaicong Xu, Hamed Heydari, Bryan Joseph San LuisErmira Shuteriqi, Hongwei Zhu, Nydia Van Dyk, Sara Sharifpoor, Michael Costanzo, Robbie Loewith, Amy Caudy, Daniel Bolnick, Grant W. Brown, Brenda J. Andrews, Charles Boone, Chad L. Myers

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

To systematically explore complex genetic interactions, we constructed ∼200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ∼100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

Original language	English (US)
Article number	aao1729
Journal	Science
Volume	360
Issue number	6386
DOIs	https://doi.org/10.1126/science.aao1729
State	Published - Apr 20 2018

Access

10.1126/science.aao1729

Fingerprint Dive into the research topics of 'Systematic analysis of complex genetic interactions'. Together they form a unique fingerprint.

Cite this

Kuzmin, E., VanderSluis, B., Wang, W., Tan, G., Deshpande, R., Chen, Y., Usaj, M., Balint, A., Usaj, M. M., Van Leeuwen, J., Koch, E. N., Pons, C., Dagilis, A. J., Pryszlak, M., Wang, J. Z. Y., Hanchard, J., Riggi, M., Xu, K., Heydari, H., ... Myers, C. L. (2018). Systematic analysis of complex genetic interactions. Science, 360(6386), [aao1729]. https://doi.org/10.1126/science.aao1729

Systematic analysis of complex genetic interactions. / Kuzmin, Elena; VanderSluis, Benjamin; Wang, Wen; Tan, Guihong; Deshpande, Raamesh; Chen, Yiqun; Usaj, Matej; Balint, Attila; Usaj, Mojca Mattiazzi; Van Leeuwen, Jolanda; Koch, Elizabeth N.; Pons, Carles; Dagilis, Andrius J.; Pryszlak, Michael; Wang, Jason Zi Yang; Hanchard, Julia; Riggi, Margot; Xu, Kaicong; Heydari, Hamed; Luis, Bryan Joseph San; Shuteriqi, Ermira; Zhu, Hongwei; Van Dyk, Nydia; Sharifpoor, Sara; Costanzo, Michael; Loewith, Robbie; Caudy, Amy; Bolnick, Daniel; Brown, Grant W.; Andrews, Brenda J.; Boone, Charles; Myers, Chad L.

In: Science, Vol. 360, No. 6386, aao1729, 20.04.2018.

Research output: Contribution to journal › Article › peer-review

Kuzmin, E, VanderSluis, B, Wang, W, Tan, G, Deshpande, R, Chen, Y, Usaj, M, Balint, A, Usaj, MM, Van Leeuwen, J, Koch, EN, Pons, C, Dagilis, AJ, Pryszlak, M, Wang, JZY, Hanchard, J, Riggi, M, Xu, K, Heydari, H, Luis, BJS, Shuteriqi, E, Zhu, H, Van Dyk, N, Sharifpoor, S, Costanzo, M, Loewith, R, Caudy, A, Bolnick, D, Brown, GW, Andrews, BJ, Boone, C & Myers, CL 2018, 'Systematic analysis of complex genetic interactions', Science, vol. 360, no. 6386, aao1729. https://doi.org/10.1126/science.aao1729

Kuzmin, Elena ; VanderSluis, Benjamin ; Wang, Wen ; Tan, Guihong ; Deshpande, Raamesh ; Chen, Yiqun ; Usaj, Matej ; Balint, Attila ; Usaj, Mojca Mattiazzi ; Van Leeuwen, Jolanda ; Koch, Elizabeth N. ; Pons, Carles ; Dagilis, Andrius J. ; Pryszlak, Michael ; Wang, Jason Zi Yang ; Hanchard, Julia ; Riggi, Margot ; Xu, Kaicong ; Heydari, Hamed ; Luis, Bryan Joseph San ; Shuteriqi, Ermira ; Zhu, Hongwei ; Van Dyk, Nydia ; Sharifpoor, Sara ; Costanzo, Michael ; Loewith, Robbie ; Caudy, Amy ; Bolnick, Daniel ; Brown, Grant W. ; Andrews, Brenda J. ; Boone, Charles ; Myers, Chad L. / Systematic analysis of complex genetic interactions. In: Science. 2018 ; Vol. 360, No. 6386.

@article{f1c4666565554d20a348cffbaf0af27b,

title = "Systematic analysis of complex genetic interactions",

abstract = "To systematically explore complex genetic interactions, we constructed ∼200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ∼100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.",

author = "Elena Kuzmin and Benjamin VanderSluis and Wen Wang and Guihong Tan and Raamesh Deshpande and Yiqun Chen and Matej Usaj and Attila Balint and Usaj, {Mojca Mattiazzi} and {Van Leeuwen}, Jolanda and Koch, {Elizabeth N.} and Carles Pons and Dagilis, {Andrius J.} and Michael Pryszlak and Wang, {Jason Zi Yang} and Julia Hanchard and Margot Riggi and Kaicong Xu and Hamed Heydari and Luis, {Bryan Joseph San} and Ermira Shuteriqi and Hongwei Zhu and {Van Dyk}, Nydia and Sara Sharifpoor and Michael Costanzo and Robbie Loewith and Amy Caudy and Daniel Bolnick and Brown, {Grant W.} and Andrews, {Brenda J.} and Charles Boone and Myers, {Chad L.}",

year = "2018",

month = apr,

day = "20",

doi = "10.1126/science.aao1729",

language = "English (US)",

volume = "360",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6386",

}

TY - JOUR

T1 - Systematic analysis of complex genetic interactions

AU - Kuzmin, Elena

AU - VanderSluis, Benjamin

AU - Wang, Wen

AU - Tan, Guihong

AU - Deshpande, Raamesh

AU - Chen, Yiqun

AU - Usaj, Matej

AU - Balint, Attila

AU - Usaj, Mojca Mattiazzi

AU - Van Leeuwen, Jolanda

AU - Koch, Elizabeth N.

AU - Pons, Carles

AU - Dagilis, Andrius J.

AU - Pryszlak, Michael

AU - Wang, Jason Zi Yang

AU - Hanchard, Julia

AU - Riggi, Margot

AU - Xu, Kaicong

AU - Heydari, Hamed

AU - Luis, Bryan Joseph San

AU - Shuteriqi, Ermira

AU - Zhu, Hongwei

AU - Van Dyk, Nydia

AU - Sharifpoor, Sara

AU - Costanzo, Michael

AU - Loewith, Robbie

AU - Caudy, Amy

AU - Bolnick, Daniel

AU - Brown, Grant W.

AU - Andrews, Brenda J.

AU - Boone, Charles

AU - Myers, Chad L.

PY - 2018/4/20

Y1 - 2018/4/20

N2 - To systematically explore complex genetic interactions, we constructed ∼200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ∼100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

AB - To systematically explore complex genetic interactions, we constructed ∼200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ∼100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

UR - http://www.scopus.com/inward/record.url?scp=85045545118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045545118&partnerID=8YFLogxK

U2 - 10.1126/science.aao1729

DO - 10.1126/science.aao1729

M3 - Article

C2 - 29674565

AN - SCOPUS:85045545118

VL - 360

JO - Science

JF - Science

SN - 0036-8075

IS - 6386

M1 - aao1729

ER -

Systematic analysis of complex genetic interactions

Abstract

Access

Other files and links

Cite this