Single-cell RNA sequencing of human tissue supports successful drug targets

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Early characterization of drug targets associated with disease can greatly reduce clinical failures attributed to lack safety or efficacy. As single-cell RNA sequencing (scRNA-seq) human tissues becomes increasingly common for profiling, the insights obtained from this data could influence target selection strategies. Whilst use scRNA-seq understand biology is well established, impact in increasing probability candidate therapeutic successfully advance research clinic has not been fully characterized. Inspired by previous work on an association between genetic evidence and success, we used retrospective analysis known genes identify potential predictors success data. Particularly, investigated whether successful are cell type specific expression a disease-relevant tissue (cell specificity) over-expression patients compared healthy controls (disease specificity). Analysing across 30 diseases 13 tissues, found that both classes support significantly increase odds gene-disease pairs. We estimate combined they approximately triple chances reaching phase III. Importantly, identifies larger complementary space direct evidence. In particular, more likely prioritize therapeutically tractable such as membrane-bound proteins. Our study suggests scRNA-seq-derived information type- disease-specific be leveraged targets, increased clinic.

Language: Английский

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Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics

Biochemistry and Biophysics Reports, Journal Year: 2023, Volume and Issue: 37, P. 101589 - 101589

Published: Nov. 29, 2023

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of together, single-cell enables uncover the heterogeneity within tumors and understand unique characteristics different cell populations. By doing so, we can identify rare subpopulations that are influential in tumor growth, metastasis, resistance therapy. Moreover, analysis provides valuable insights into immune response triggered various therapeutic interventions, such as checkpoint blockade, chemotherapy, It also helps better intricate microenvironment its impact on patient prognosis treatment. This comprehensive review focuses recent advancements methodologies, with an emphasis technologies. highlights important role these techniques uncovering complexity tumorigenesis multiple applications research, well their equally great contributions other areas immunology. Through multi-omics, gain deeper understanding biology pave way for more precise effective strategies. Apart from those above, this paper aims introduce live imaging technology, latest developments protein detection techniques, explore seamless integration technology.

Language: Английский

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Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: Nov. 29, 2022

COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe critical. Severe critical patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about epigenetic alterations that occur these cells during hyperinflammatory responses patients. In this study, we obtained DNA methylome transcriptome peripheral blood monocytes samples extracted CD14 + CD15- 48 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. parallel, single-cell transcriptomics 10 generated. CellPhoneDB was used infer crosstalk between other immune cell types. We observed methylation CpG sites associated interferon-related genes antigen presentation, concordant gene expression changes. These significantly overlapped those occurring bacterial sepsis, although specific viral infection also identified. found comprise some differentiation under influence inflammatory cytokines. A progression relation Sequential Organ Failure Assessment (SOFA) score be related T-helper 1 cytokine production. analysis transcriptomes types suggested existence altered like NK regulatory T cells. Our findings show occurrence an transcriptional reprogramming monocytes, which could release aberrant immature increased systemic levels pro-inflammatory cytokines,

Language: Английский

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Long COVID-19 outcomes of patients with pre-existing dementia

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Although COVID-19 has been linked to worse acute outcomes in patients with some neurodegenerative disorders, its long-term impact on dementia remains unclear.

Language: Английский

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Φ-Space: Continuous phenotyping of single-cell multi-omics data

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract Single-cell multi-omics technologies have empowered increasingly refined characterisation of the heterogeneity cell populations. Automated type annotation methods been developed to transfer labels from well-annotated reference datasets emerging query datasets. However, these suffer some common caveats, including failure characterise transitional and novel states, sensitivity batch effects under-utilisation phenotypic information other than types (e.g. sample source disease conditions). We Φ-Space, a computational framework for continuous phenotyping single-cell data. In Φ-Space we adopt highly versatile modelling strategy continuously identity in low-dimensional phenotype space, defined by phenotypes. The space embedding enables various downstream analyses, insightful visualisations, clustering labelling. demonstrate through three case studies that (i) characterises developing out-of-reference states; (ii) is robust against both query; (iii) adapts tasks involving multiple omics types; (iv) overcomes technical differences between query. versatility makes it applicable wide range analytical beyond transfer, its ability model complex variation will facilitate biological discoveries different types.

Language: Английский

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Potenzial und Anwendungsmöglichkeiten der Analyse einzelner Zellen: Hochauflösende Analytik

Trillium Diagnostik, Journal Year: 2024, Volume and Issue: 22(3), P. 166 - 168

Published: Sept. 13, 2024

Die Analyse von Einzelzellen birgt großes Potenzial für die Diagnostik und Therapie verschiedenster Erkrankungen. In der Onkologie werden bereits im Rahmen Liquid Biopsy einzelne zirkulierende Tumorzellen Blut charakterisiert, um Krankheitsverläufe zu überwachen oder optimal anzupassen. Weiterentwicklung Einzelzellanalyse beispielsweise durch Spatial-Omics-Technologien sowie bioinformatische Auswertung verschiedener Informationsebenen lässt hoffen, dass in Zukunft bei komplexen physiologischen Prozessen pathogene Abweichungen nur wenigen Zellen frühzeitig identifiziert können.

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Understanding the impact of COVID-19 on quality of life using surveys and Mendelian randomization

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 28, 2024

The COVID-19 pandemic has significantly impacted the quality of life (QoL) individuals in China, affecting both their physical and mental well-being. This study aims to comprehensively analyze factors influencing QoL China during pandemic. In 2022, we collected data using a self-developed questionnaire (dataset 2) obtained dataset 1 from 2021 General Social Survey (CGSS). After confirming scale's reliability validity, employed random forest algorithm prioritize factors. Subsequently, Mendelian randomization analyses were conducted MRC IEU OpenGWAS infrastructure. By comparing two periods with low high infection rates, results showed that among various influences brought about by prevalence COVID-19, sleep disorders have significant widespread impact on life, especially for elderly. Through inclusion analysis, found relative increase risk developing insomnia approximately 26.7% (OR = 1.267). These findings can inform development targeted interventions strategies improve overall

Language: Английский

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