Exact association test for small size sequencing data

Abstract

BackgroundRecent statistical methods for next generation sequencing (NGS) data have been successfully applied to identifying rare genetic variants associated with certain diseases. However, most commonly used methods (e.g., burden tests and variance-component tests) rely on large sample sizes. Notwithstanding, due to its-still high cost, NGS data is generally restricted to small sample sizes, that cannot be analyzed by most existing methods.MethodsIn this work, we propose a new exact association test for sequencing data that does not require a large sample approximation, which is applicable to both common and rare variants. Our method, based on the Generalized Cochran-Mantel-Haenszel (GCMH) statistic, was applied to NGS datasets from intraductal papillary mucinous neoplasm (IPMN) patients. IPMN is a unique pancreatic cancer subtype that can turn into an invasive and hard-to-treat metastatic disease.ResultsApplication of our method to IPMN data successfully identified susceptible genes associated with progression of IPMN to pancreatic cancer. ConclusionsOur method is expected to identify disease-associated genetic variants more successfully, and corresponding signal pathways, improving our understanding of specific disease’s etiology and prognosis.

SNP Alleles Associated With Low Bolting Tendency in Sugar Beet

“…(Supplementary Figure 1). Several other studies using similar test statistics resulted in the identification of good causal markers (Liang et al, 2016;Yang et al, 2016;Lee et al, 2018). While we confirmed the strong association of two markers in this study on three validation datasets containing contrasting bolting phenotypes, we were also able to identify and map candidate genes related to vernalization responsiveness, flowering time, and floral development through bioinformatics analyses (Supplementary Table 2).…”

“…Mining the most useful SNPs discriminating the phenotypes involved the use of both (a) Fisher exact test and (b) nbinom test from DESeq2 to identify SNP signatures strongly linked to bolting tolerance post-winter ( Supplementary Figure 1 ). Several other studies using similar test statistics resulted in the identification of good causal markers (Liang et al, 2016 ; Yang et al, 2016 ; Lee et al, 2018 ).…”

“…The genotype matrix was analyzed using the SNPRelate package in R to build PCA plots and understand the genetic structure ( Figure 2 ). For the genome-wide association analyses, the genotypes for each of the SNP markers were reduced to allele frequencies using the genetics package in R. Statistical Fisher test of independence using custom R scripts (attached as Supplementary Text 2 ) was then conducted to test the difference of partial association of genotypes in two strata of contingency tables, corresponding to two groups of bolters and non-bolters (Liang et al, 2016 ; Yang et al, 2016 ; Lee et al, 2018 ). Manhattan plots to visualize the data were generated using the qqman package in R ( Figure 3 ).…”

A Counterstory to Deficit Narratives of “Underperformance” of Demographically Minoritized Students in General Chemistry

“…Fisher's Exact Test for Count Data is a statistical test that adequately handles count data with low Ns. 89 The results have a Cramer's V = 0.26, which represents a moderate effect size. In Figure 5 we observe that both Latine and Black students are less likely to obtain grades in the Letter A range.…”

How does the coral, Pocillopora acuta, survive the challenging intertidal environment? A genome-wide analysis

“…SNPs with association p values of [? ]0.01 were considered significantly associated with intertidal P. acuta colonies (Lee et al, 2018;Llinares-Lo pez et al, 2015;Purcell et al, 2007). Results were visualized with a Manhattan plot using ggplot2 and qqman packages in R (Turner, 2018;Wickham, 2016).…”