Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(6), P. 1578 - 1578

Published: May 25, 2018

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation active compounds. Modern medicine however, requires the and purification one two There however a lot global health challenges with diseases such cancer, degenerative diseases, HIV/AIDS diabetes, which modern is struggling to provide cures. times "active compound" has made compound ineffective. Drug discovery multidimensional problem requiring several parameters both natural synthetic compounds safety, pharmacokinetics efficacy be evaluated during drug candidate selection. advent latest technologies that enhance design hypotheses Artificial Intelligence, use 'organ-on chip' microfluidics technologies, means automation become part discovery. This resulted in increased speed evaluation whilst allowing novel ways synthesis based on Recent advances analytical computational techniques opened new avenues process complex products their structures derive innovative drugs. Indeed, we era molecular design, applied products. Predictive softwares contributed targets derivatives. In future quantum computing, databases modelling interactions predicting features needed for development, pharmacokinetic pharmacodynamics, will result few false positive leads development. review discusses plant-based product how play role next-generation

Language: Английский

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Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer

Cell, Journal Year: 2018, Volume and Issue: 174(3), P. 758 - 769.e9

Published: July 1, 2018

Language: Английский

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Genomic basis for RNA alterations in cancer

Nature, Journal Year: 2020, Volume and Issue: 578(7793), P. 129 - 136

Published: Feb. 5, 2020

Abstract Transcript alterations often result from somatic changes in cancer genomes 1 . Various forms of RNA have been described cancer, including overexpression 2 , altered splicing 3 and gene fusions 4 ; however, it is difficult to attribute these underlying genomic owing heterogeneity among patients tumour types, the relatively small cohorts for whom samples analysed by both transcriptome whole-genome sequencing. Here we present, our knowledge, most comprehensive catalogue cancer-associated date, obtained characterizing transcriptomes 1,188 donors Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA) 5 Using matched sequencing data, associated several categories with germline DNA alterations, identified probable genetic mechanisms. Somatic copy-number were major drivers variations total allele-specific expression. We 649 associations single-nucleotide variants expression cis which 68.4% involved flanking non-coding regions gene. found 1,900 mutations, formation exons within introns proximity Alu elements. In addition, 82% structural variants, 75 a new class, termed ‘bridged’ fusions, third location bridges two genes. observed transcriptomic alteration signatures that differ between types mutational signatures. This compendium context provides rich resource identifying genes mechanisms are functionally implicated cancer.

Language: Английский

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Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 13, 2021

Abstract The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding heterogeneity. We performed nucleus ATAC (snATAC-seq) RNA (snRNA-seq) sequencing to generate paired, cell-type-specific transcriptional profiles the adult human kidney. demonstrate that snATAC-seq is comparable snRNA-seq in assignment identity can further refine our functional heterogeneity nephron. majority differentially accessible regions are localized promoters significant proportion closely associated with expressed genes. Cell-type-specific enrichment transcription factor binding motifs implicates activation NF-κB promotes VCAM1 expression drives transition between subpopulation proximal tubule epithelial cells. Our multi-omics approach improves ability detect unique states within kidney redefines cellular thick ascending limb.

Language: Английский

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An atlas of dynamic chromatin landscapes in mouse fetal development

Nature, Journal Year: 2020, Volume and Issue: 583(7818), P. 744 - 751

Published: July 29, 2020

The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling diverse panel mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state accessibility in developing fetus. In total performed 1,128 immunoprecipitation with sequencing (ChIP-seq) assays histone modifications 132 assay transposase-accessible using (ATAC-seq) across 72 distinct tissue-stages. We used integrative analysis to develop unified set annotations, infer identities dynamic enhancers key transcriptional regulators, characterize relationship between during gene regulation. also leveraged these data link putative target genes demonstrate tissue-specific enrichments sequence variants associated disease humans. ENCODE sets provide compendium resources biomedical researchers achieve, our knowledge, most comprehensive view dynamics fetal development date.

Language: Английский

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The GeneCards Suite

Published: Jan. 1, 2021

Abstract The GeneCards ® database of human genes was launched in 1997 and has expanded since then to encompass gene-centric, disease-centric, pathway-centric entities relationships within the Suite, effectively navigating universe biological data—genes, proteins, cells, regulatory elements, pathways, diseases—and connections among them. knowledgebase amalgamates information from >150 selected sources related genes, ncRNAs, chemical compounds, drugs, splice variants, SNPs, signaling molecules, differentiation protocols, stem genetic tests, clinical trials, diseases, publications, more empowers suite’s Next Generation Sequencing (NGS), gene set, shared descriptors, batch query analysis tools.

Language: Английский

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EnhancerAtlas 2.0: an updated resource with enhancer annotation in 586 tissue/cell types across nine species

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: unknown

Published: Oct. 31, 2019

Enhancers are distal cis-regulatory elements that activate the transcription of their target genes. They regulate a wide range important biological functions and processes, including embryogenesis, development, homeostasis. As more large-scale technologies were developed for enhancer identification, comprehensive database is highly desirable annotation based on various genome-wide profiling datasets across different species. Here, we present an updated EnhancerAtlas 2.0 (http://www.enhanceratlas.org/indexv2.php), covering 586 tissue/cell types include large number normal tissues, cancer cell lines, cells at development stages nine Overall, contains 13 494 603 enhancers, which obtained from 16 055 using 12 high-throughput experiment methods (e.g. H3K4me1/H3K27ac, DNase-seq/ATAC-seq, P300, POLR2A, CAGE, ChIA-PET, GRO-seq, STARR-seq MPRA). The version huge expansion first version, only enhancers in human cells. In addition, predicted enhancer-target gene relationships human, mouse fly. Finally, users can search through five user-friendly, interactive modules. We believe new will facilitate to perform useful functional analysis genomes.

Language: Английский

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Mapping and characterization of structural variation in 17,795 human genomes

Nature, Journal Year: 2020, Volume and Issue: 583(7814), P. 83 - 89

Published: May 27, 2020

Language: Английский

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A genomic and epigenomic atlas of prostate cancer in Asian populations

Nature, Journal Year: 2020, Volume and Issue: 580(7801), P. 93 - 99

Published: March 25, 2020

Language: Английский

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Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(9), P. 969 - 983

Published: Aug. 24, 2020

Language: Английский

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