Cited by 870Fungal and yeast genetics researchBioinformatics and Genomic NetworksCellular transport and secretion

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Exploration of the Function and Organization of the Yeast Early Secretory Pathway through an Epistatic Miniarray Profile

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Schuldiner, Maya, Collins, Sean R., Thompson, Natalie J., Denic, Vladimir, Bhamidipati, Arunashree, Punna, Thanuja, Ihmels, Jan, Andrews, Brenda, Boone, Charles, Greenblatt, Jack F., Weissman, Jonathan S., Krogan, Nevan J.·2005·Cell

DOI 10.1016/j.cell.2005.08.031

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Abstract

We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by focusing on logically connected gene subsets and including essential genes. Described here is the analysis of an E-MAP of genes acting in the yeast early secretory pathway. Hierarchical clustering, together with novel analytical strategies and experimental verification, revealed or clarified the role of many proteins involved in extensively studied processes such as sphingolipid metabolism and retention of HDEL proteins. At a broader level, analysis of the E-MAP delineated pathway organization and components of physical complexes and illustrated the interconnection between the various secretory processes. Extension of this strategy to other logically connected gene subsets in yeast and higher eukaryotes should provide critical insights into the functional/organizational principles of biological systems.

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Role of Hsp70 in Post-Translational Protein Targeting: Tail-Anchored Membrane Proteins and Beyond
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“One of the most exciting developments in experimental data for large-scale function prediction has been technology, such as SGA [29], dSLAM [21] and E-MAP [ 26 ], that can produce high-throughput screens of massive numbers of pairwise mutant combinations.”
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Self-citation
Network Clustering Analysis Using Mixture Exponential-Family Random Graph Models and Its Application in Genetic Interaction Data
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“or adopt hierarchical cluster analysis which use the correlation between genetic interaction profiles as a measure of functional association [5].”
Background
Systematic Gene-to-Phenotype Arrays: A High-Throughput Technique for Molecular Phenotyping
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Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats
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Metabolic Flux Correlations, Genetic Interactions, and Disease
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“Comparison with experimental data is feasible due to related high-throughput experimental methods of SGA (Tong et al., 2004), dSLAM (Pan et al., 2004), and EMAP (Schuldiner et al., 2005), with over 14,585 interactions deposited in the BioGRID database (Stark et al., 2006).”
Method
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BackgroundMethodInfluential
Yeast phospholipid biosynthesis is linked to mRNA localization
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Genetic interaction screens advance in reversePreprint
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“Analogous methods have been used to discover synthetic genetic interactions involving essential genes using the collection of strains with tet-inducible genes (Davierwala et al. 2005) and the DAmP collection with destabilized transcripts (Schuldiner et al. 2005).”
BackgroundMethod
Asna1/TRC40 that mediates membrane insertion of tail-anchored proteins is required for efficient release of Herpes simplex virus 1 virions
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Background
The metabolite-controlled ubiquitin conjugase Ubc8 promotes mitochondrial protein import
Rödl, S., den Brave, F., Räschle, M., Kizmaz, B., Lenhard, S., Groh, C., Becker, H., Zimmermann, J., Morgan, B., Richling, E., et al. (2022) · Life Science Alliance · doi:10.26508/lsa.202201526 · Cited by 12
“Using automated mating approaches, the Oxa1-Ura3 expression cassette was introduced into yeast libraries covering 4,916 deletion mutants of nonessential genes and 1,102 DAmP (decreased abundance by mRNA perturbation) mutants of essential genes (Schuldiner et al, 2005; Hansen et al, 2018).”
Dynamic stability of Sgt2 enables selective and privileged client handover in a chaperone triad
Cho, H.-J., Liu, Y., Chung, S., Chandrasekar, S., Weiss, S., & Shan, S. (2024) · Nature Communications · doi:10.1038/s41467-023-44260-5 · Cited by 9
Genes involved in novel adaptive aluminum resistance in Rhodotorula glutinis
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‘Domino’ systems biology and the ‘A’ of ATP
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“This contention is supported by an estimate of more than 150 processes needed together for life to be sustainable [8].”
Background
Genetic interaction analysis of point mutations enables interrogation of gene function at a residue‐level resolution
Braberg, H., Moehle, E. A., Shales, M., Guthrie, C., & Krogan, N. J. (2014) · BioEssays · doi:10.1002/bies.201400044 · Cited by 9
“This technique, termed epistatic miniarray profile (E-MAP) [10, 17, 18], enabled the quantitative collection of Figure 1.”
BackgroundMethodSelf-citation
Functional genomics in the study of yeast cell polarity: moving in the right direction
Styles, E. B., Youn, J., Ušaj, M. M., & Andrews, B. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0118 · Cited by 9
Self-citation
Yeast Gup1(2) Proteins Are Homologues of the Hedgehog Morphogens Acyltransferases HHAT(L): Facts and Implications
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A Visual Framework for Classifying Determinants of Cell Size
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“Notably, the extent of the upshift in cells with solely increased mRNA transcription from multiple mCherry-DAmP (Schuldiner et al., 2005) copies was similar to the changes in protein-expressing cells with the same growth defect, suggesting that increased size is independent of protein accumulation…”
Background
Coordinated Roles of the Putative Ceramide-Conjugation Protein, Cwh43, and a Mn2+-Transporting, P-Type ATPase, Pmr1, in Fission Yeast
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“In addition, budding yeast CWH43 and PER1 show genetic interaction with a cation-transporting P-type ATPase, SPF1 (Schuldiner et al. 2005; Surma et al. 2013; Costanzo et al. 2016).”
Background
Genetic interactions derived from high-throughput phenotyping of 6589 yeast cell cycle mutants
Gallegos, J. E., Adames, N. R., Rogers, M. F., Kraikivski, P., Ibele, A., Nurzynski-Loth, K., Kudlow, E., Murali, T. M., Tyson, J. J., & Peccoud, J. (2020) · npj Systems Biology and Applications · doi:10.1038/s41540-020-0134-z · Cited by 9
“…increasing the number of biological replicates to eight from four in a standard E-MAP or one in a standard SGA (which use technical replicates 29,30 gene i ::kanMX refers to gene i knocked-out with a kanamycin-resistance marker, gene i ::natMX refers to gene i knocked-out with a…”
BackgroundMethodInfluential
Automated data integration for developmental biological research
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DETECTION OF DISJOINT AND OVERLAPPING MODULES IN WEIGHTED COMPLEX NETWORKS
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A quantitative analysis of monochromaticity in genetic interaction networks
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“The other methodology, called epistatic miniarray profile (E-MAP), is based on measuring the growth rates of single mutant strains and double mutants [11].”
BackgroundMethod

Authors: Schuldiner, M., Collins, S. R., Thompson, N. J., Denic, V., Bhamidipati, A., Punna, T., Ihmels, J., Andrews, B., Boone, C., Greenblatt, J. F., Weissman, J. S., & Krogan, N. J.
Affiliations: Howard Hughes Medical Institute (US)
University of Toronto (CA)
Corresponding author: Weissman, Jonathan S.
ORCID: Schuldiner, Maya
Collins, Sean R.
Denic, Vladimir
Andrews, Brenda
Boone, Charles
Weissman, Jonathan S.
Krogan, Nevan J.
Venue: Cell
Publisher: Elsevier BV
Published: 2005-11
Volume: 123
Issue: 3
Pages: 507-519
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2005.08.031
OpenAlex: W2042688172
Cited by: 870
References: 45
Citations by year: 2026: 12 · 2025: 12 · 2024: 15 · 2023: 19 · 2022: 23 · 2021: 30 · 2020: 34 · 2019: 30 · 2018: 36 · 2017: 41 · 2016: 25 · 2015: 47 · 2014: 54 · 2013: 57 · 2012: 61
FWCI: 20.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2815 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords: genetic interaction mapping, sphingolipid metabolism, protein complex formation, essential genes, hierarchical clustering, Saccharomyces cerevisiae
MeSH terms: Endoplasmic Reticulum, Epistasis, Genetic, Glycosylation, Membrane Proteins, Mutation, Saccharomyces cerevisiae, Cluster Analysis, Receptors, Peptide, Computational Biology, Gene Expression Profiling, Protein Transport, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins

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Exploration of the Function and Organization of the Yeast Early Secretory Pathway through an Epistatic Miniarray Profile

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