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Transcriptional profiling of Mycobacterium tuberculosis exposed to proton pump inhibitor treatment in broth culture.

ABSTRACT: Transcriptional profiling of Mycobacterium tuberculosis exposed to proton pump inhibitor treatment in broth culture.

PROVIDER: PRJNA1238329 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32778600.fastq.gz	Fastqsanger.gz
	SRR32778601.fastq.gz	Fastqsanger.gz
	SRR32778602.fastq.gz	Fastqsanger.gz
	SRR32778603.fastq.gz	Fastqsanger.gz
	SRR32778604.fastq.gz	Fastqsanger.gz

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Transcriptional profiling of Mycobacterium tuberculosis exposed to proton pump inhibitor treatment in broth culture.

Project description:We hypothesized that an improved Mtb TRN could be inferred using a large, diverse compendium of RNA-seq data and therefore sought to supplement the existing repository of Mtb expression data available on SRA with additional conditions that could inform on Mtb's underlying regulatory programs. We profiled Mtb transcriptional response to a range of different proton bump inhibitor exposures in 7H9 broth culture by RNA-seq. Compound abbreviations: (PAN = pantoprazole, RAB = rabeprazole, VER = verapamil, LAN = lansoprazole, OMP = omeprazole). We went on to infer Mtb's TRN using a collection of inference methods in combination with this compendium, and employed it to build an interpretable machine learning model of Mtb fitness under stress.

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Project description:Regorafenib is a novel oral multi-kinase inhibitor which targets angiogenic, stromal and oncogenic receptor tyrosine kinases. It is currently registered for GIST and mCRC. When regorafenib is co-administered with an acid suppressive agent, the intra-gastric pH increases, and as a result the equilibrium of ionized/non-ionized regorafenib may shift to the less soluble non-ionized form which reduces regorafenib bioavailability and exposure. Since proton pump inhibitors (PPIs) are often used during regorafenib therapy, this drug-drug interaction (DDI) confronts pharmacists and oncologists with challenges in clinical practice. In this study the investigators will therefore evaluate the impact of PPI-induced intra-gastric pH elevation on regorafenib pharmacokinetics in patients with GIST and mCRC.

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RNAseq analyses of Esophageal biopsies from proton pump inhibitor (PPI)-responsive and PPI-unresponsive Pediatric patients with Eosinophilic Esophagitis.

Project description:Clinical trials have identified two distinct eosinophilic esophagitis (EoE) treatment phenotypes, proton pump inhibitor (PPI)-responsive (PPI-R) and PPI-unresponsive (PPI-UR). Herein, we performed clinical, endoscopic, and histologic evaluation of esophageal biopsies from pediatric PPI-R and PPI-UR EoE individuals prior to PPI therapy (diagnosis) and following PPI trial. RNAseq analyses of esophageal biopsy samples revealed common immune and inflammatory transcriptional signatures in both PPI-R EoE and PPI-UR EoE at diagnosis and distinct signatures enriched for processes related to neuropeptide signaling and cell cycle and division. PPI therapy induced histologic, endoscopic, and transcriptional remission in PPI-R EoE, but not in PPI-UR EoE. Persistent disease in PPI-UR EoE was associated with the presence of Th2 inflammatory and dedifferentiated esophageal epithelial transcriptomic signatures, while PPI-R EoE revealed genes enriched in cellular responses to LPS, host defense to viruses and type-I interferon signaling. In silico analyses identified common and unique EoE disease gene drivers in PPI-R and PPI-UR EoE. These studies indicate that the two EoE phenotypes have unique transcriptomic elements that underlie the molecular nature of PPI-R and PPI-UR EoE disease.

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Expression data from young and senescent HCAECs treated with proton pump inhibitors (omeprazole and lansoprazole)

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