mRNAs, proteins and the emerging principles of gene expression control

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(10), P. 630 - 644

Published: July 24, 2020

Language: Английский

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Confronting false discoveries in single-cell differential expression

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

Published: Sept. 28, 2021

Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available identify differentially expressed genes, principles that distinguish these and their performance remain unclear. Here, we show relative is contingent on ability account for variation between biological replicates. Methods ignore this inevitable biased prone false discoveries. Indeed, most widely used can discover hundreds genes absence differences. To exemplify principles, exposed true discoveries injured mouse spinal cord.

Language: Английский

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Next-Generation Sequencing Technology: Current Trends and Advancements

Biology, Journal Year: 2023, Volume and Issue: 12(7), P. 997 - 997

Published: July 13, 2023

The advent of next-generation sequencing (NGS) has brought about a paradigm shift in genomics research, offering unparalleled capabilities for analyzing DNA and RNA molecules high-throughput cost-effective manner. This transformative technology swiftly propelled advancements across diverse domains. NGS allows the rapid millions fragments simultaneously, providing comprehensive insights into genome structure, genetic variations, gene expression profiles, epigenetic modifications. versatility platforms expanded scope facilitating studies on rare diseases, cancer genomics, microbiome analysis, infectious population genetics. Moreover, enabled development targeted therapies, precision medicine approaches, improved diagnostic methods. review provides an insightful overview current trends recent technology, highlighting its potential impact areas genomic research. delves challenges encountered future directions including endeavors to enhance accuracy sensitivity data, novel algorithms data pursuit more efficient, scalable, solutions that lie ahead.

Language: Английский

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RNA sequencing: new technologies and applications in cancer research

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Dec. 1, 2020

Abstract Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk to single-molecular, single-cell and spatial approaches enabled increasingly accurate, individual cell resolution incorporated with information. Cancer, major malignant heterogeneous lethal disease, remains an enormous challenge in medical research clinical treatment. As vital tool, been utilized many aspects of cancer therapy, including biomarker discovery characterization heterogeneity evolution, drug resistance, immune microenvironment immunotherapy, neoantigens so on. In this review, latest studies on technology their applications are summarized, future challenges opportunities discussed.

Language: Английский

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From bulk, single-cell to spatial RNA sequencing

International Journal of Oral Science, Journal Year: 2021, Volume and Issue: 13(1)

Published: Nov. 15, 2021

Abstract RNA sequencing (RNAseq) can reveal gene fusions, splicing variants, mutations/indels in addition to differential expression, thus providing a more complete genetic picture than DNA sequencing. This most widely used technology genomics tool box has evolved from classic bulk (RNAseq), popular single cell (scRNAseq) newly emerged spatial (spRNAseq). Bulk RNAseq studies average global scRNAseq investigates biology up 20,000 individual cells simultaneously, while spRNAseq ability dissect activities spatially, representing next generation of article highlights these technologies, characteristic features and suitable applications precision oncology.

Language: Английский

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Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(6), P. 389 - 406

Published: Jan. 25, 2022

Language: Английский

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Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(632)

Published: Feb. 16, 2022

Nociceptors are specialized sensory neurons that detect damaging or potentially stimuli and found in the dorsal root ganglia (DRG) trigeminal ganglia. These critical for generation of neuronal signals ultimately create perception pain. also primary targets treating acute chronic Single-cell transcriptomics on mouse nociceptors has transformed our understanding pain mechanisms. We sought to generate equivalent information human with goal identifying transcriptomic signatures nociceptors, species differences potential drug targets. used spatial molecularly characterize transcriptomes single DRG from eight organ donors. identified 12 clusters neurons, 5 which C as well 1 low-threshold mechanoreceptors (LTMRs), Aβ nociceptor, 2 Aδ, Aβ, proprioceptor subtypes. By focusing expression profiles ion channels, G protein-coupled receptors (GPCRs), other pharmacological targets, we provided a rich map direct comparison neuron transcriptomes. compared subtypes nonhuman primates showing conserved patterns gene among many cell types but divergence specific nociceptor subsets. Last, sex subpopulation transcriptomes, including marked increase calcitonin-related polypeptide alpha (CALCA) female pruritogen receptor-enriched nociceptors. This comprehensive characterization might open door development better treatments disorders.

Language: Английский

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Chromatin accessibility profiling by ATAC-seq

Nature Protocols, Journal Year: 2022, Volume and Issue: 17(6), P. 1518 - 1552

Published: April 27, 2022

Language: Английский

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Improved transcriptome assembly using a hybrid of long and short reads with StringTie

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(6), P. e1009730 - e1009730

Published: June 1, 2022

Short-read RNA sequencing and long-read each have their strengths weaknesses for transcriptome assembly. While short reads are highly accurate, they rarely able to span multiple exons. Long-read technology can capture full-length transcripts, but its relatively high error rate often leads mis-identified splice sites. Here we present a new release of StringTie that performs hybrid-read By taking advantage the both long reads, assembly with is more accurate than only or short-read assembly, on some datasets it double number correctly assembled while obtaining substantially higher precision data alone. demonstrate improved accuracy simulated real from Arabidopsis thaliana , Mus musculus human. We also show correcting prior being faster. freely available as open source software at https://github.com/gpertea/stringtie .

Language: Английский

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The role of alternative splicing in cancer: From oncogenesis to drug resistance

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100728 - 100728

Published: Sept. 28, 2020

Alternative splicing is a tightly regulated process whereby non-coding sequences of pre-mRNA are removed and protein-coding segments assembled in diverse combinations, ultimately giving rise to proteins with distinct or even opposing functions. In the past decade, whole genome/transcriptome sequencing studies revealed high complexity regulation, which occurs co-transcriptionally influenced by chromatin status mRNA modifications. Consequently, profiles both healthy malignant cells display diversity alternative was shown be widely deregulated multiple cancer types. particular, mutations regulatory sequences, regulators modifiers, as well differential expression factors important contributors pathogenesis. It has become clear that these aberrations contribute many facets cancer, including oncogenic transformation, progression, response anticancer drug treatment resistance therapy. this respect, perturb broad spectrum relevant genes involved uptake/metabolism (i.e. SLC29A1, dCK, FPGS, TP), activation nuclear receptor pathways GR, AR), regulation apoptosis MCL1, BCL-X, FAS) modulation immunotherapy (CD19). Furthermore, aberrant constitutes an source novel biomarkers spliceosome machinery represents attractive target for rapidly expanding class therapeutic agents. Small molecule inhibitors targeting SF3B1 splice factor kinases were highly cytotoxic against wide range models, drug-resistant cells. Importantly, effects enhanced specific subsets, such factor-mutated c-MYC-driven tumors. pre-clinical report synergistic modulators combination conventional antitumor These strategies based on use low dose could shift window towards decreased toxicity tissues. Here we provide extensive overview latest findings field molecular mechanisms harness drive oncogenesis evade splicing-based vulnerabilities can opportunities. discuss current challenges arising from genome-wide detection prediction methods splicing, unravelling functional relevance plethora cancer-related alterations.

Language: Английский

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