SLIM: a sliding linear model for estimating the proportion of true null hypotheses in datasets with dependence structures

Wang, Shaoyi; Tuominen, Lindsey K.; Tsai, Chung‐Jui

doi:10.1093/bioinformatics/btq650

Cited by 204 publications

(156 citation statements)

References 14 publications

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“…Hypo/hypermethylated regions covered by at least 10 reads with percentage methylation difference larger than 25% were identified using q-value , 0.01. Fisher's exact test was used to calculate P values, and P values were adjusted to q-values using the SLIM method (Wang et al, 2011). The location and function of genes in the soybean genome version Wm82.a2.v1 were downloaded from Phytozome (Goodstein et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

The Methylome of Soybean Roots during the Compatible Interaction with the Soybean Cyst Nematode

et al. 2015

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ORCID IDs: 0000-0003-4046-1672 (J.H.R.); 0000-0003-4082-9502 (T.L.); 0000-0003-2971-9353 (M.S.).The soybean cyst nematode (SCN; Heterodera glycines) induces the formation of a multinucleated feeding site, or syncytium, whose etiology includes massive gene expression changes. Nevertheless, the genetic networks underlying gene expression control in the syncytium are poorly understood. DNA methylation is a critical epigenetic mark that plays a key role in regulating gene expression. To determine the extent to which DNA methylation is altered in soybean (Glycine max) roots during the susceptible interaction with SCN, we generated whole-genome cytosine methylation maps at single-nucleotide resolution. The methylome analysis revealed that SCN induces hypomethylation to a much higher extent than hypermethylation. We identified 2,465 differentially hypermethylated regions and 4,692 hypomethylated regions in the infected roots compared with the noninfected control. In addition, 703 and 1,346 unique genes were identified as overlapping with hyper-or hypomethylated regions, respectively. The differential methylation in genes apparently occurs independently of gene size and GC content but exhibits strong preference for recently duplicated paralogs. Furthermore, a set of 278 genes was identified as specifically syncytium differentially methylated genes. Of these, we found genes associated with epigenetic regulation, phytohormone signaling, cell wall architecture, signal transduction, and ubiquitination. This study provides, to our knowledge, new evidence that differential methylation is part of the regulatory mechanisms controlling gene expression changes in the nematode-induced syncytium.

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Section: Discussionmentioning

confidence: 99%

The Methylome of Soybean Roots during the Compatible Interaction with the Soybean Cyst Nematode

et al. 2015

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“…For each CpG, the proportions of methylated reads in the two photoperiods were compared using the Fisher's exact test, and the P-values were corrected to genomic-wide false discovery rate (FDR)-based Q-values by using the SLIM method (Wang et al 2011). The methylated sites were mapped to genes using custom Perl scripts.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

DNA methylation changes induced by long and short photoperiods inNasonia

et al. 2015

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Many organisms monitor the annual change in day length and use this information for the timing of their seasonal response. However, the molecular mechanisms underlying photoperiodic timing are largely unknown. The wasp Nasonia vitripennis is an emerging model organism that exhibits a strong photoperiodic response: Short autumnal days experienced by females lead to the induction of developmental arrest (diapause) in their progeny, allowing winter survival of the larvae. How female Nasonia control the developmental trajectory of their offspring is unclear. Here, we took advantage of the recent discovery that DNA methylation is pervasive in Nasonia and tested its role in photoperiodism. We used reduced representation bisulfite sequencing (RRBS) to profile DNA methylation in adult female wasps subjected to different photoperiods and identified substantial differential methylation at the single base level. We also show that knocking down DNA methyltransferase 1a (Dnmt1a), Dnmt3, or blocking DNA methylation pharmacologically, largely disrupts the photoperiodic diapause response of the wasps. To our knowledge, this is the first example for a role of DNA methylation in insect photoperiodic timing.

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“…The forward and reverse strand CpG site coverage essentially represent the same CpG sites; we have combined forward and reverse coverage by setting the DESTRAND = True parameter in methylKit package (default = False). Differentially methylated CpG sites were identified using methylKit algorithm [59] that used logistic regression to calculate p-values, adjusted the p-values for multiple hypothesis testing and generated q values using SLIM approach [60]. The criteria used for identification of differentially methylated CpG sites was q-value of < 0.01 and a percent methylation difference ≥ 25% for each individual CpG site.…”

Section: Analysis Of Differential Dna Methylationmentioning

confidence: 99%

Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended ‘male sex drive’ hypothesis

Chatterjee

Lagisz

Rodger

et al. 2016

Gene

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Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive ' hypothesis, Gene (2016' hypothesis, Gene ( ), doi: 10.1016' hypothesis, Gene ( /j.gene.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3 ABSTRACTThe sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain.Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis.Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time.

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SLIM: a sliding linear model for estimating the proportion of true null hypotheses in datasets with dependence structures

Abstract: The R code of the proposed method is available at http://aspendb.uga.edu/downloads for academic use.

Cited by 204 publications

References 14 publications

The Methylome of Soybean Roots during the Compatible Interaction with the Soybean Cyst Nematode

The Methylome of Soybean Roots during the Compatible Interaction with the Soybean Cyst Nematode

DNA methylation changes induced by long and short photoperiods inNasonia

Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended ‘male sex drive’ hypothesis

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