7 research outputs found
Mutual Enrichment in Ranked Lists and the Statistical Assessment of Position Weight Matrix Motifs
Statistics in ranked lists is important in analyzing molecular biology
measurement data, such as ChIP-seq, which yields ranked lists of genomic
sequences. State of the art methods study fixed motifs in ranked lists. More
flexible models such as position weight matrix (PWM) motifs are not addressed
in this context. To assess the enrichment of a PWM motif in a ranked list we
use a PWM induced second ranking on the same set of elements. Possible orders
of one ranked list relative to the other are modeled by permutations. Due to
sample space complexity, it is difficult to characterize tail distributions in
the group of permutations. In this paper we develop tight upper bounds on tail
distributions of the size of the intersection of the top of two uniformly and
independently drawn permutations and demonstrate advantages of this approach
using our software implementation, mmHG-Finder, to study PWMs in several
datasets.Comment: Peer-reviewed and presented as part of the 13th Workshop on
Algorithms in Bioinformatics (WABI2013
LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
Abstract Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basalâlike subtype associates with increased EGFR signaling, while another, the HER2âenriched subtype, engages a kin of EGFR. Based on the premise that EGFRâregulated lncRNAs might control the aggressiveness of basalâlike tumors, we identified multiple EGFRâinducible lncRNAs in basalâlike normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basalâlike and in HER2âpositive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers
LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basalâlike subtype associates with increased EGFR signaling, while another, the HER2âenriched subtype, engages a kin of EGFR. Based on the premise that EGFRâregulated lncRNAs might control the aggressiveness of basalâlike tumors, we identified multiple EGFRâinducible lncRNAs in basalâlike normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basalâlike and in HER2âpositive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers
LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basalâlike subtype associates with increased EGFR signaling, while another, the HER2âenriched subtype, engages a kin of EGFR. Based on the premise that EGFRâregulated lncRNAs might control the aggressiveness of basalâlike tumors, we identified multiple EGFRâinducible lncRNAs in basalâlike normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basalâlike and in HER2âpositive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers