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Chromatin-informed inference of transcriptional programs in gynecologic cancers [RNA-Seq]

ABSTRACT: Chromatin-informed inference of transcriptional programs in gynecologic cancers [RNA-Seq]

PROVIDER: PRJNA530973 | ENA |

REPOSITORIES: ENA

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Chromatin-informed inference of transcriptional programs in gynecologic cancers

Project description:Chromatin-informed inference of transcriptional programs in gynecologic cancers

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Chromatin-informed inference of transcriptional programs in gynecologic cancers [ATAC-Seq]

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Chromatin-informed inference of transcriptional programs in gynecologic cancers [ATAC-Seq]

Project description:Epigenomic data on transcription factor occupancy and chromatin accessibility can elucidate the developmental origin of cancer cells and reveal the enhancer landscape of key oncogenic transcriptional regulators. However, in many cancers, epigenomic analyses have been limited, and computational methods to infer regulatory networks in tumors typically use expression data alone, or rely on transcription factor (TF) motifs in annotated promoter regions. Here, we develop a novel machine learning strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to combine cell line chromatin accessibility data with large tumor expression data sets and model the effect of enhancers on transcriptional programs in multiple cancers. We generated a new ATAC-seq data set profiling chromatin accessibility in gynecologic and basal breast cancer cell lines and applied PSIONIC to 723 RNA-seq experiments from ovarian, uterine, and basal breast tumors as well as 96 cell line RNA-seq profiles. Our computational framework enables us to share information across tumors to learn patient-specific inferred TF activities, revealing regulatory differences between and within tumor types. Many of the identified TF regulators were significantly associated with survival outcome in basal breast, uterine serous and endometrioid carcinomas. Moreover, PSIONIC-predicted activity for MTF1 in cell line models correlated with sensitivity to MTF1 inhibition. Therefore computationally dissecting the role of TFs in gynecologic cancers may ultimately advance personalized therapy.

2019-05-01 | GSE114964 | GEO

Chromatin-informed inference of transcriptional programs in gynecologic cancers

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-05-01 | GSE129339 | GEO

Chromatin-informed inference of transcriptional programs in gynecologic cancers [RNA-Seq]

Project description:RNA-seq of MDA-MB-436 cells in control cells (shRen) and upon knockdown of MITF ( shQa, sh962) were generated by deep sequencing in duplicates

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Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers.

Project description:Chromatin accessibility data can elucidate the developmental origin of cancer cells and reveal the enhancer landscape of key oncogenic transcriptional regulators. We develop a computational strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to combine chromatin accessibility data with large tumor expression data and model the effect of enhancers on transcriptional programs in multiple cancers. We generate a new ATAC-seq data profiling chromatin accessibility in gynecologic and basal breast cancer cell lines and apply PSIONIC to 723 patient and 96 cell line RNA-seq profiles from ovarian, uterine, and basal breast cancers. Our computational framework enables us to share information across tumors to learn patient-specific TF activities, revealing regulatory differences between and within tumor types. PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome. To validate PSIONIC-derived prognostic TFs, we perform immunohistochemical analyses in 31 uterine serous tumors for ETV6 and 45 basal breast tumors for MITF and confirm that the corresponding protein expression patterns are also significantly associated with prognosis.

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Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

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Preoperatively Walking’s Effect of Postoperative Bowel Functions in Patient With Gynecologic Cancer.

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2021-09-01 | GSE157601 | GEO

Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers

Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers

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