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eQTL Mapping for Functional Classes of Saccharomyces cerevisiae Genes with Multivariate Sparse Partial Least Squares Regression

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Handbook of Statistical Bioinformatics

Part of the book series: Springer Handbooks of Computational Statistics ((SHCS))

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Abstract

The availability of high-throughput genotyping technologies and microarray assays has enabled investigation of genetic variations that influence levels of gene expression. Expression Quantitative Trait Loci (eQTL) mapping methods have been successfully used to identify the genetic basis of gene expression which in turn led to identification of candidate genes and construction of regulatory networks. One challenging statistical aspect of eQTL mapping is the existence of thousands of traits. We have recently proposed a multivariate sparse partial least squares framework for mapping multiple quantitative traits and identifying genetic variations that affect the expression of a group of genes. In this book chapter, we provide a comprehensive illustration of this methodology with a Saccharomyces cerevisiae linkage study. Data from this study involves segregants from a cross between two Saccharomyces cerevisiae strains. Our application focuses on elucidating genomic markers that affect expression of functional yeast gene classes. We illustrate identification of eQTL regions affecting whole functional classes of genes as well as eQTL regions influencing individual genes.

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References

  1. Alifano, P., Fani, R., Liò, P., Lazcano, A., Bazzicalupo, M., Carlomagno, M., & Bruni, C. (1996). Histidine biosynthetic pathway and genes: Structure, regulation, and evolution. Microbiological Reviews, 60, 44–69.

    Google Scholar 

  2. Allison, D. B., Thiel, B., Jean, P. S., Elston, R. C., Infante, M. C., & Schork, N. J. (1998). Multiple phenotype modeling in gene-mapping studies of quantitative traits: Power advantages. American Journal of Human Genetics, 63, 1190–1201.

    Article  Google Scholar 

  3. Andreadis, A., Hsu, Y., Hermodson, M., Kohlhaw, G., & Schimmel, P. (1984). Yeast LEU2. Repression of mRNA levels by leucine and primary structure of the gene product. The Journal of Biological Chemistry, 259, 8059–8062.

    Google Scholar 

  4. Bhat, P., & Murthy, T. (2001). Transcriptional control of the GAL/MEL regulon of yeast Saccharomyces cerevisiae: Mechanism of galactose-mediated signal transduction. Molecular Microbiology, 40, 1059–1066.

    Article  Google Scholar 

  5. Brem, R., & Kruglyak, L. (2005). The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proceedings of the National Academy of Sciences of the United States of America, 102, 1572–1577.

    Article  Google Scholar 

  6. Brem, R., Storey, J., Whittle, J., & Kruglyak, L. (2005). Genetic interactions between polymorphisms that affect gene expression in yeast. Nature, 436, 701–703.

    Article  Google Scholar 

  7. Brem, R., Yvert, G., Clinton, R., & Kryglyak, L. (2002). Genetic dissection of transcriptional regulation in budding yeast. Science, 296, 752–755.

    Article  Google Scholar 

  8. Broman, K. W., Wu, H., Sen, S., & Churchill, G. A. (2003). R/qtl: QTL mapping in experimental crosses. Bioinformatics, 19, 889–890.

    Article  Google Scholar 

  9. Chen, M., & Kendziorski, C. (2007). A statistical framework for expression quantitative trait loci (eQTL) mapping. Genetics, 177, 761–771.

    Article  Google Scholar 

  10. Chen, W., Balzi, E., Capieaux, E., Choder, M., & Goffeau, A. (1991). The DNA sequencing of the 17 kb HindIII fragment spanning the LEU1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae reveals the PDR6 gene, a new member of the genetic network controlling pleiotropic drug resistance. Yeast, 7, 287–299.

    Article  Google Scholar 

  11. Chesler, E. J., Lu, L., Shou, S., Qu, Y., Gu, J., Wang, J., Hsu, H. C., Mountz, J. D., Baldwin, N. E., Langston, M. A., Threadgill, D. W., Manly, K. F., & Williams, R. W. (2005). Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nature Genetics, 37(4), 233–242.

    Article  Google Scholar 

  12. Chun, H., & Keleş, S. (2009). Expression quantitative trait loci mapping with multivariate sparse partial least squares regression. Genetics, 182, 79–90.

    Article  Google Scholar 

  13. Chun, H., & Keleş, S. (2010). Sparse partial least squares for simultaneous dimension reduction and variable selection. Journal of the Royal Statistical Society: Series B, 72, 3–25.

    Article  Google Scholar 

  14. Dwight, S. S., Balakrishnan, R., Christie, K. R., Costanzo, M. C., Dolinski, K., Engel, S. R., Feierbach, B., Fisk, D. G., Hirschman, J., Hong, E. L., Issel-Tarver, L., Nash, R. S., Sethuraman, A., Starr, B., Theesfeld, C. L., Andrada, R., Binkley, G., Dong, Q., Lane, C., Schroeder, M., Weng, S., Botstein, D., & Cherry, J. M. (2004). Saccharomyces genome database: Underlying principles and organisation. Briefings in Bioinformatics, 5(1), 922. http://dx.doi.org/10.1093/bib/5.1.9

  15. Felder, T., Bogengruber, E., Tenreiro, S., Ellinger, A., Sá-Correia, I., & Briza, P. (2002). Dtrlp, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae. Eukaryotic cell, 1, 799–810.

    Article  Google Scholar 

  16. Gasch, A., & Eisen, M. (2002). Exploring the conditional coregulation of yeast gene expression through fuzzy k-means clustering. Genome Biology, 3, research0059.1”0059.22.

    Google Scholar 

  17. Gbelska, Y., Krijger, J., & Breunig, K. (2006). Evolution of gene families: The multidrug resistance transporter genes in five related yeast species. FEMS Yeast Research, 6, 345–355.

    Article  Google Scholar 

  18. Gelfond, J. A. L., Ibrahim, J. G., & Zou, F. (2007). Proximity model for expression quantitative trait loci (eQTL) detection. Biometrics, 63(4), 1108–1116.

    Article  MathSciNet  MATH  Google Scholar 

  19. Harbison, C., Gordon, D., Lee, T., Rinaldi, N., Macisaac, K., Danford, T., Hannett, N., Tagne, J. B., Reynolds, D., Yoo, J., Jennings, E., Zeitlinger, J., Pokholok, D., Kellis, M., Rolfe, P., Takusagawa, K., Lander, E., Gifford, D., Fraenkel, E., & Young, R. (2004). Transcriptional regulatory code of a eukaryotic genome. Nature, 431, 99–104.

    Article  Google Scholar 

  20. Herskowitz, I. (1989). A regulatory hierarchy for cell specialization in yeast. Nature, 342, 749–757.

    Article  Google Scholar 

  21. Jia, Z., & Xu, S. (2007). Mapping quantitative trait loci for expression abundance. Genetics, 176, 611–623.

    Article  Google Scholar 

  22. Jiang, C., & Zeng, Z. (1995). Multiple trait analysis of genetic mapping for quantitative trait loci. Genetics, 140, 1111–1127.

    Google Scholar 

  23. Jiang, D., Tang, C., & Zhang, A. (2004). Cluster analysis for gene expression data: A survey. IEEE Transactions on Knowledge and Data Engineering, 16(11), 1370–1386.

    Article  Google Scholar 

  24. Karpichev, I. V., & Small, G. M. (1998). Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Molecular Cell Biology, 18, 6560–6570.

    Google Scholar 

  25. Keesey, J. J., Bigelis, R., & Fink, G. (1979). The product of the his4 gene cluster in Saccharomyces cerevisiae. a trifunctional polypeptide. The Journal of Biological Chemistry, 254, 7427–7433.

    Google Scholar 

  26. Kendziorski, C., & Wang, P. (2006). A review of statistical methods for expression quantitative trait loci mapping. Mammalian Genome, 17(6), 509–517.

    Article  Google Scholar 

  27. Kendziorski, C. M., Chen, M., Yuan, M., Lan, H., & Attie, A. D. (2006). Statistical methods for expression quantitative trait loci (eQTL) mapping. Biometrics, 62, 19–27.

    Article  MathSciNet  MATH  Google Scholar 

  28. Keng, T., Richard, C., & Larocque, R. (1992). Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Molecular and General Genetics, 234, 233–243.

    Google Scholar 

  29. Kim, K. W., Kamerud, J. Q., Livingston, D. M., & Roon, R. (1988). Asparaginase II of Saccharomyces cerevisiae. Characterization of the ASP3 gene. Journal of Biological Chemistry, 263, 11948–11953.

    Google Scholar 

  30. Kohlhaw, G. (2003). Leucine biosynthesis in fungi: Entering metabolism through the back door. Microbiology and Molecular Biology Reviews, 67, 1–15.

    Article  Google Scholar 

  31. Lan, H., Chen, M., Flowers, J. B., Yandell, B. S., Stapleton, D. S., Mata, C. M., n Keen Mui, E. T., Flowers, M. T., Schueler, K. L., Manly, K. F., Williams, R. W., Kendziorski, C., & Attie, A. D. (2006). Combined expression trait correlations and expression quantitative trait locus mapping. PLoS Genetics, 2, e6.

    Google Scholar 

  32. Lan, H., Stoehr, J. P., Nadler, S. T., Schueler, K. L., Yandell, B. S., & Attie, A. D. (2003). Dimension reduction for mapping mRNA abundance as quantitative traits. Genetics, 164, 1607–1614.

    Google Scholar 

  33. Li, J., & Burmeister, M. (2005). Human molecular genetics review issue 2. BMC Genomics, 14(2), R163–R169.

    Google Scholar 

  34. Morley, M., Molony, C. M., Weber, T. M., Devlin J. L. snd Ewens, K. G., Spielman, R. S., & Cheung, V. G. (2004). Genetic analysis of genome-wide variation in human gene expression. Nature, 430(7001), 743–747.

    Google Scholar 

  35. Platt, A., & Reece, R. (1998). The yeast galactose genetic switch is mediated by the formation of a Gal4p-Gal80p-Gal3p complex. The EMBO Journal, 17, 4086–4091.

    Article  Google Scholar 

  36. Rottensteiner, H., Kal, A. J., Hamilton, B., Ruis, H., & Tabak, H. F. (1997). A heterodimer of the Zn2Cys6 transcription factors Pip2p and Oaf1p controls induction of genes encoding peroxisomal proteins in Saccharomyces cerevisiae. European Journal of Biochemistry, 247, 776–783.

    Article  Google Scholar 

  37. Saerens, S., Verstrepen, K., Van Laere, S., Voet, A., Van Dijck, P., Delvaux, F., & Thevelein, J. (2006). The Saccharomyces cerevisiae EHT1 and EEB1 genes encode novel enzymes with medium-chain fatty acid ethyl ester synthesis and hydrolysis capacity. The Journal of Biological Chemistry, 281, 4446–4456.

    Article  Google Scholar 

  38. Schadt, E. E., Monks, S. A., Drake, T., Lusis, A. J., Che, N., Colinayo, V., Ruff, T. G., Milligan, S. B., Lamb, J. R., Cavet, G., Linsley, P. S., Mao, M., Stoughton, R. B., & Friend, S. H. (2003). Genetics of gene expression surveyed in maize, mouse and man. Nature, 422, 297–302.

    Article  Google Scholar 

  39. Schreve, J., Sin, J., & Garrett, J. (1998). The Saccharomyces cerevisiae YCC5 (YCL025c) gene encodes an amino acid permease, Agp1, which transports asparagine and glutamine. Journal of Bacteriology, 180, 2556–2559.

    Google Scholar 

  40. Stranger, B. E., Forrest, M. S., Clark, A. G., Minichiello, M. J., Deutsch, S., Lyle, R., Hunt, S., Kahl, B., Antonarakis, S. E., Tavare, S., Deloukas, P., & Dermitzakis, E. T. (2005). Genome-wide associations of gene expression variation in humans. PLoS Genetics, 1(6), e78.

    Article  Google Scholar 

  41. Sun, W., Yu, T., & Li, K. C. (2007). Detection of eQTL modules mediated by activity levels of transcription factors. Bioinformatics, 23, 2290–2297.

    Article  Google Scholar 

  42. Sun, W., Yuan, S., & Li, K. C. (2008). Trait-trait dynamic interaction: 2D-trait eQTL mapping for genetic variation study. BMC Genomics, 9, 242.

    Article  Google Scholar 

  43. Tenreiro, S., Nunes, P., Viegas, C., Neves, M., Teixeira, M., Cabral, M., & Sá-Correia, I. (2002). AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae. Biochemical and Biophysical Research Communications, 292, 741–748.

    Article  Google Scholar 

  44. Troyanskaya, O., Cantor, M., Sherlock, G., Brown, P., Hastie, T., Tibshirani, R., Botstein, D., & Altman, R. B. (2001). Missing value estimation methods for DNA microarrays. Bioinformatics, 17, 520–525.

    Article  Google Scholar 

  45. Velasco, I., Tenreiro, S., Calderon, I., & André, B. (2004). Saccharomyces cerevisiae Aqr1 is an internal-membrane transporter involved in excretion of amino acids. Eukaryotic Cell, 3, 1492–1503.

    Article  Google Scholar 

  46. Wang, S., Yehya, N., Schadt, E. E., Wang, H., Drake, T. A., & Lusis, A. J. (2006). Genetic and genomic analysis of a fat mass trait with complex inheritance reveals marked sex specificity. PLoS Genetics, 2(2), e15.

    Article  Google Scholar 

  47. Wang, Y., & Dohlman, H. (2004). Pheromone signaling mechanisms in yeast: A prototypical sex machine. Science, 306, 1508–1509.

    Article  Google Scholar 

  48. Wu, C., Delano, D. L., Mitro, N., Su, S. V., Janes, J., McClurg, P., Batalov, S., Welch, G. L., Zhang, J., Orth, A. P., Walker, J. R., Glynne, R. J., Cooke, M. P., Takahashi, J. S., Shimomura, K., Kohsaka, A., Bass, J., Saez, E., Wiltshrie, T., & Su, A. I. (2008). Gene set enrichment in eQTL identifies novel annotations and pathway regulators. PLoS Genetics, 4(5), e1000,070.

    Google Scholar 

  49. Yvert, G., Brem, R. B., Whittle, J., Akey, J. M., Foss, E., Smith, E. N., Mackelprang, R., & Kruglyak, L. (2003). Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nature Genetics, 35, 57–64.

    Article  Google Scholar 

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Acknowledgements

This research was supported by NSF grant DMS 0804597 to SK.

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Correspondence to Sündüz Keleş .

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Chung, D., Keleş, S. (2011). eQTL Mapping for Functional Classes of Saccharomyces cerevisiae Genes with Multivariate Sparse Partial Least Squares Regression. In: Lu, HS., Schölkopf, B., Zhao, H. (eds) Handbook of Statistical Bioinformatics. Springer Handbooks of Computational Statistics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16345-6_13

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