Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 M-BM-5M), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms. Genome DNA from IP resistant strains vs. Reference 3D7 or Dd2

2011-10-31 | E-GEOD-32485 | biostudies-arrayexpress

Targeted Next-generation Sequencing Panel for Identification of Germline Mutations in Early Onset Cancers With Sporadic or Hereditary Presentation

Project description:Despite relevant clinical and/or familial presentations suggesting a hereditary predisposition (early-onset, multiple primary tumors, familial aggregation), targeted genomic analysis based on the phenotype are often non contributive. As somatic cancer genes are limited, the hypothesis is that the targeted next-generation sequencing of 200 genes, selected for their implications in cancers may contribute to the understanding of many selected patients’ presentation by the identification of germline deleterious mutations, and may identified phenotype overlapping and/or mosaicisms. The focus will be put on early-onset breast, ovarian, colorectal cancer or pediatric cancers and multiple primary tumors.

| 2206884 | ecrin-mdr-crc

A MicroRNA Next-Generation-Sequencing Discovery Assay (miND) For Genome-Scale and Absolute Quantitation of Circulating MicroRNA Biomarkers

Project description:The plasma levels of tissue-specific microRNAs can be used as prognostic and diagnostic biomarkers for chronic and acute diseases. Thereby, the combination of diverse miRNAs into biomarker signatures using multivariate statistics seems especially powerful in view to tissue and condition specific miRNA shedding into the plasma. Although Next-Generation Sequencing (NGS) technology enables to analyse circulating microRNAs on a genome-scale level, it suffers from potential biases (e.g. adapter ligation bias) and lacks absolute transcript quantitation. In order to develop a robust NGS discovery assay for genome-scale quantitation of circulating microRNAs we first evaluated the sensitivity, repeatability and ligation bias of four commercially available small RNA library preparation protocols. The protocol from RealSeq Biosciences was selected based on its performance and usability, and coupled with a novel panel of exogenous small RNA spike-in controls to enable absolute quantitation and ensure comparability of data across independent NGS experiments. The established MicroRNA Next-Generation-Sequencing Discovery Assay (miND) was validated for its relative accuracy, precision, analytical measurement range and sequencing bias and was considered fit-for-purpose for microRNA biomarker discovery. Summarized, all these criteria were met and thus our analytical platform is considered fit-for-purpose for microRNA biomarker discovery from plasma, serum, cerebrospinal fluid (CSF), synovial fluid (SF), or extracellular vesicles (EV) extracted from cell culture medium in the setting of any diagnostic, prognostic or patient stratification need.

2022-01-20 | GSE189930 | GEO

Next-Generation Antimicrobial Discovery through Bacterial Self-Screening of Surface-Displayed Peptide Libraries

Project description:Next-Generation Antimicrobial Discovery through Bacterial Self-Screening of Surface-Displayed Peptide Libraries

| PRJNA371422 | ENA

Next generation sequence analysis

Project description:Next generation sequence analysis

| PRJNA560769 | ENA

Next Generation Mendelian Genetics: Familial Hemophagocytic Lymphohistiocytosis

Project description:The NHGRI Next Generation Mendelian Genetics project uses exome resequencing to identify variants in unsolved Mendelian diseases. Familial hemophagocytic lymphohistiocytosis (fHLH) is a serious immune disorder that results from defective cytotoxic lymphocyte function. Autosomal recessive mutations in PFP1, UNC13D, STX11, STBP2, or RAB27, and hemizygous mutations in SH2D1A or BIRC4, account for known causes of the disease, but 30-70% of patients in North America lack a known genetic etiology. This project was designed to identify additional genetic abnormalities from HLH patients. The exome sequences of four unrelated individuals with a diagnosis of HLH, but without mutations in genes known to cause disease, were obtained by massively parallel DNA sequencing.

| phs000537.v1.p1 | EGA

Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery

Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 µM), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.

2011-10-31 | GSE32485 | GEO

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