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Graham McVicker edited QTL testing with WASP.tex
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\section{Discovery of quantitative trait loci with WASP}
To discover molecular quantitative trait loci (QTLs) WASP uses a statistical test, which we call the Combined Haplotype Test (CHT). As input, CHT takes genotype probabilities at known SNPs as well as mapped reads from
next-generation sequencing sequencing-based experiments such as ChIP-seq or RNA-seq. CHT combines two types of
information from next generation sequencing data: information: the depth of mapped reads and the allelic imbalance of mapped reads that overlap heterozygous sites. CHT models the overdispersion of read counts (both across regions and across individuals) and accounts for variability introduced by GC content and the fraction of reads that fall within peaks.
We used an early version of CHT to discover histone mark QTLs \cite{McVicker_2013}. We have since extended the statistical model and
made numerous improvements to improved the software implementation. These improvements include:
\begin{itemize}
\item Automatic estimation of dispersion parameters from the data,
\item Adjustment for unknown covariates by allowing principal component loadings to be provided,