Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach

Journal Article · Fri Jul 12 04:00:00 EDT 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.05.138· OSTI ID:22239661

Han, Sangjo ^[1]; Lee, Minho ^[2]; Chang, Hyeshik ^[3]; Nam, Miyoung ^[4]; Park, Han-Oh ^[5]; Kwak, Youn-Sig ^[6]; Ha, Hye-jeong ^[7]; Kim, Dongsup ^[2]; Hwang, Sung-Ook ^[8]; Hoe, Kwang-Lae ^[4]; Kim, Dong-Uk ^[7]

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1. Bioinformatics Lab, Healthcare Group, SK Telecom, 9-1, Sunae-dong, Pundang-gu, Sungnam-si, Kyunggi-do 463-784 (Korea, Republic of)
2. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of)
3. Department of Biological Science, Seoul National University, 599 Gwanakro, Gwanak-gu, Seoul 151-747 (Korea, Republic of)
4. Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764 (Korea, Republic of)
5. Bioneer Corp., 8-11 Munpyeongseo-ro, Daedeok-gu, Daejeon 306-220 (Korea, Republic of)
6. Department of Applied Biology, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 660-701 (Korea, Republic of)
7. Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-Gu, Daejeon 305-806 (Korea, Republic of)
8. Department of Obstetrics and Gynecology, Inha University Hospital, 7-206 Sinheung-dong, Jung-gu, Incheon 400-711 (Korea, Republic of)

Highlights: •The first compendium of chemical-genetic profiles form fission yeast was generated. •The first HTS of drug mode-of-action in fission yeast was performed. •The first comparative chemical genetic analysis between two yeasts was conducted. -- Abstract: Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at (http://pombe.kaist.ac.kr/compendium)

• OSTI ID: 22239661
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 436; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
DNA
DRUGS
FUNGICIDES
GENES
HIGH-TC SUPERCONDUCTORS
PONDS
PROTEINS
SACCHAROMYCES CEREVISIAE
SENSITIVITY