TY - JOUR
T1 - Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile
AU - Schuldiner, Maya
AU - Collins, Sean R.
AU - Thompson, Natalie J.
AU - Denic, Vladimir
AU - Bhamidipati, Arunashree
AU - Punna, Thanuja
AU - Ihmels, Jan
AU - Andrews, Brenda
AU - Boone, Charles
AU - Greenblatt, Jack F.
AU - Weissman, Jonathan S.
AU - Krogan, Nevan J.
N1 - Funding Information:
We thank M. Noble for help with strain construction; E. Kannegaard for help developing the DAmP system; J. Newman for help with FACS analysis; S. Munro and F. Barr for communicating results prior to publication; H. Ding, K. Vachon, L. Le, C. Sun, K. Chin, Z. Hassam, X. Wu, M. Lim, T. Chan, J. Rilestone, and K. Takhar for help with screens; Affinium Pharmaceuticals for mass spectrometry; R. Parker for helpful discussions regarding the DAmP strategy; F. Winston, J. Ingles, K. Tipton, S. Ghaemmaghami, D. Cameron, and O. Schuldiner for discussions and critical reading of the manuscript; and A. DePace for help with graphics. We would like to thank H. Dieter Schmitt, P. Walter, and M. Rose for reagents. This work was supported by funds from HHMI (J.S.W.), the HFSP (M.S.), the Burroughs Wellcome Foundation (S.R.C.), the Ontario Genomics Institute and Genome Canada (J.F.G., B.A., and C.B.), and the CIHR (C.B., N.J.K., and B.A.).
PY - 2005/11/4
Y1 - 2005/11/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=26844489762&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2005.08.031
DO - 10.1016/j.cell.2005.08.031
M3 - Article
C2 - 16269340
AN - SCOPUS:26844489762
SN - 0092-8674
VL - 123
SP - 507
EP - 519
JO - Cell
JF - Cell
IS - 3
ER -