Regmex, Motif analysis in ranked lists of sequences

Mm, Nielsen; Tataru, Paula; Madsen, Tobias; Hobolth, Asger; Js, Pedersen

doi:10.1101/035956

Cited by 3 publications

(1 citation statement)

References 20 publications

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“…A motif enrichment analysis tool, Regmex, capable of using regular expression, was used to analyze whether the differentially expressed genes in the siRNA analysis contained motifs (words) with perfect match(es) to the seed regions of siRNA_1 and siRNA_2 (Nielsen et al., 2016). In brief, Regmex evaluates enrichment of motifs in ranked lists of sequences by calculating a per sequence p ‐value for finding the observed number of motifs or more in a sequence, using a Markov chain embedding approach.…”

Section: Methodsmentioning

confidence: 99%

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

et al. 2016

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It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA‐sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up‐regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt‐regulated transcription factors, including ASCL2, ETS2, and c‐Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO‐CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) “sponging” miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3′UTR of Stearoyl‐CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down‐regulated upon SNHG16 silencing. In conclusion, up‐regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms.

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Section: Methodsmentioning

confidence: 99%

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

et al. 2016

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Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival

et al. 2018

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Cancer develops by accumulation of somatic driver mutations, which impact cellular function. Mutations in non-coding regulatory regions can now be studied genome-wide and further characterized by correlation with gene expression and clinical outcome to identify driver candidates. Using a new two-stage procedure, called ncDriver, we first screened 507 ICGC whole-genomes from 10 cancer types for non-coding elements, in which mutations are both recurrent and have elevated conservation or cancer specificity. This identified 160 significant non-coding elements, including the TERT promoter, a well-known non-coding driver element, as well as elements associated with known cancer genes and regulatory genes (e.g., PAX5, TOX3, PCF11, MAPRE3). However, in some significant elements, mutations appear to stem from localized mutational processes rather than recurrent positive selection in some cases. To further characterize the driver potential of the identified elements and shortlist candidates, we identified elements where presence of mutations correlated significantly with expression levels (e.g., TERT and CDH10) and survival (e.g., CDH9 and CDH10) in an independent set of 505 TCGA whole-genome samples. In a larger pan-cancer set of 4128 TCGA exomes with expression profiling, we identified mutational correlation with expression for additional elements (e.g., near GATA3, CDC6, ZNF217, and CTCF transcription factor binding sites). Survival analysis further pointed to MIR122, a known marker of poor prognosis in liver cancer. In conclusion, the screen for significant mutation patterns coupled with correlative mutational analysis identified new individual driver candidates and suggest that some non-coding mutations recurrently affect expression and play a role in cancer development.

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Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival

Hornshøj

Nielsen

Sinnott‐Armstrong

et al. 2017

Preprint

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Cancer develops by accumulation of somatic driver mutations, which impact cellular function. Noncoding mutations in non-coding regulatory regions can now be studied genome-wide and further characterized by correlation with gene expression and clinical outcome to identify driver candidates. Using a new two-stage procedure, called ncDriver, we first screened 507 ICGC wholegenomes from ten cancer types for non-coding elements, in which mutations are both recurrent and have elevated conservation or cancer specificity. This identified 160 significant non-coding elements, including the TERT promoter, a well-known non-coding driver element, as well as elements associated with known cancer genes and regulatory genes (e.g., PAX5, TOX3, PCF11, MAPRE3). However, in some significant elements, mutations appear to stem from localized mutational processes rather than recurrent positive selection in some cases. To further characterize the driver potential of the identified elements and shortlist candidates, we identified elements where presence of mutations correlated significantly with expression levels (e.g. TERT and CDH10) and survival (e.g. CDH9 and CDH10) in an independent set of 505 TCGA whole-genome samples. In a larger pan-cancer set of 4,128 TCGA exomes with expression profiling, we identified mutational correlation with expression for additional elements (e.g., near GATA3, CDC6, ZNF217 and CTCF transcription factor binding sites). Survival analysis further pointed to MIR122, a known marker of poor prognosis in liver cancer. This screen for significant mutation patterns followed by correlative mutational analysis identified new individual driver candidates and suggest that some non-coding mutations recurrently affect expression and play a role in cancer development.

show abstract

Regmex, Motif analysis in ranked lists of sequences

Cited by 3 publications

References 20 publications

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival

Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival

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