Browsing by Author "Wang, Tzi-Yuan"

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A simple method using Pyrosequencing (TM) to identify de novo SNPs in pooled DNA samples
(2011-03-01)
Lin, Yeong-Shin
;
Liu, Fu-Guo Robert
;
Wang, Tzi-Yuan
;
Pan, Cheng-Tsung
;
Chang, Wei-Ting
A practical way to reduce the cost of surveying single-nucleotide polymorphism (SNP) in a large number of individuals is to measure the allele frequencies in pooled DNA samples. Pyrosequencing (TM) has been frequently used for this application because signals generated by this approach are proportional to the amount of DNA templates. The Pyrosequencing (TM) pyrogram is determined by the dispensing order of dNTPs, which is usually designed based on the known SNPs to avoid asynchronistic extensions of heterozygous sequences. Therefore, utilizing the pyrogram signals to identify de novo SNPs in DNA pools has never been undertook. Here, in this study we developed an algorithm to address this issue. With the sequence and pyrogram of the wild-type allele known in advance, we could use the pyrogram obtained from the pooled DNA sample to predict the sequence of the unknown mutant allele (de novo SNP) and estimate its allele frequency. Both computational simulation and experimental Pyrosequencing(TM) test results suggested that our method performs well. The web interface of our method is available at http://life.nctu.edu.tw/similar to yslin/PSM/.
Natural selection on cis and trans regulation in yeasts
(2010-06-01)
Emerson, J. J.
;
Hsieh, Li-Ching
;
Sung, Huang-Mo
;
Wang, Tzi-Yuan
;
Huang, Chih-Jen
Gene expression is regulated both by cis elements, which are DNA segments closely linked to the genes they regulate, and by trans factors, which are usually proteins capable of diffusing to unlinked genes. Understanding the patterns and sources of regulatory variation is crucial for understanding phenotypic and genome evolution. Here, we measure genome-wide allele-specific expression by deep sequencing to investigate the patterns of cis and trans expression variation between two strains of Saccharomyces cerevisiae. We propose a statistical modeling framework based on the binomial distribution that simultaneously addresses normalization of read counts derived from different parents and estimating the cis and trans expression variation parameters. We find that expression polymorphism in yeast is common for both cis and trans, though trans variation is more common. Constraint in expression evolution is correlated with other hallmarks of constraint, including gene essentiality, number of protein interaction partners, and constraint in amino acid substitution, indicating that both cis and trans polymorphism are clearly under purifying selection, though trans variation appears to be more sensitive to selective constraint. Comparing interspecific expression divergence between S. cerevisiae and S. paradoxus to our intraspecific variation suggests a significant departure from a neutral model of molecular evolution. A further examination of correlation between polymorphism and divergence within each category suggests that cis divergence is more frequently mediated by positive Darwinian selection than is trans divergence.