Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(5), P. 758 - 766

Published: May 1, 2024

Language: Английский

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Machine learning integrative approaches to advance computational immunology

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: June 11, 2024

Abstract The study of immunology, traditionally reliant on proteomics to evaluate individual immune cells, has been revolutionized by single-cell RNA sequencing. Computational immunologists play a crucial role in analysing these datasets, moving beyond traditional protein marker identification encompass more detailed view cellular phenotypes and their functional roles. Recent technological advancements allow the simultaneous measurements multiple components—transcriptome, proteome, chromatin, epigenetic modifications metabolites—within single including spatial contexts within tissues. This led generation complex multiscale datasets that can include multimodal from same cells or mix paired unpaired modalities. Modern machine learning (ML) techniques for integration “omics” data without need extensive independent modelling each modality. review focuses recent ML integrative approaches applied immunological studies. We highlight importance methods creating unified representation collections, particularly profiling technologies. Finally, we discuss challenges holistic how they will be instrumental development common coordinate framework studies, thereby accelerating research enabling discoveries computational immunology field.

Language: Английский

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Accurate aging clocks based on accumulating stochastic variation

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 30, 2023

Aging clocks have provided one of the most significant recent breakthroughs in biology aging. Such allow determination chronological and increasingly also biological age, which is prerequisite for assessing effectiveness interventions aging process preventive treatments age-related diseases. The advanced are based on age-dependent changes DNA methylation pattern. reproducibility such over life course has reinvigorated debate whether a programmed underlies A process, however, incompatibly with evolutionary theory occurs as consequence vanishing force selective pressure post-reproduction no fitness benefit by immortality soma. In fact, stochastic events been observed to occur during process. Here, we test could be built entirely variation. We find that accumulating variation sufficient accurately predict age. Moreover, current compatible random alterations or transcriptomic patterns. Our analysis unifies clock measure predicts any set data ground state at age zero used building accurate clocks.

Language: Английский

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Mapping Human Immunity and the Education of Waldeyer's Ring

Annual Review of Genomics and Human Genetics, Journal Year: 2024, Volume and Issue: 25(1), P. 161 - 182

Published: April 10, 2024

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding the immune system, providing unprecedented insight into diversity cells present throughout body their function health disease. Waldeyer's ring is collective name for lymphoid tissue aggregations upper aerodigestive tract, comprising palatine, pharyngeal (adenoids), lingual, tubal tonsils. These tonsils are first sentinels encountered by ingested inhaled antigens responsible mounting wave adaptive response. An effective mucosal response critical to neutralizing infection airway preventing systemic spread, dysfunctional responses can result ear, nose, throat pathologies. This review uses demonstrate how being applied advance system highlight directions future research.

Language: Английский

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Multiplexing cortical brain organoids for the longitudinal dissection of developmental traits at single-cell resolution

Nature Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Dissecting human neurobiology at high resolution and with mechanistic precision requires a major leap in scalability, given the need for experimental designs that include multiple individuals and, prospectively, population cohorts. To lay foundation this, we have developed benchmarked complementary strategies to multiplex brain organoids by pooling cells from different pluripotent stem cell (PSC) lines either during organoid generation (mosaic models) or before single-cell RNA sequencing (scRNA-seq) library preparation (downstream multiplexing). We also new computational method, SCanSNP, consensus call deconvolve identities, overcoming current criticalities doublets low-quality identification. validated both multiplexing methods charting neurodevelopmental trajectories resolution, thus linking specific individuals' genetic variation. Finally, modeled their scalability across combinations showed mosaic represent an enabling method high-throughput settings. Together, this suite of provides highly scalable resource disease neurodiversity modeling.

Language: Английский

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Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Mental disorders are a representative type of brain disorder, including anxiety, major depressive depression (MDD), and autism spectrum disorder (ASD), that caused by multiple etiologies, genetic heterogeneity, epigenetic dysregulation, aberrant morphological biochemical conditions. Psychedelic drugs such as psilocybin lysergic acid diethylamide (LSD) have been renewed fascinating treatment options gradually demonstrated potential therapeutic effects in mental disorders. However, the multifaceted conditions psychiatric resulting from individuality, complex interplay, intricate neural circuits impact systemic pharmacology psychedelics, which disturbs integration mechanisms may result dissimilar medicinal efficiency. The precise prescription psychedelic remains unclear, advanced approaches needed to optimize drug development. Here, recent studies demonstrating diverse pharmacological psychedelics reviewed, emerging perspectives on structural function, microbiota-gut-brain axis, transcriptome discussed. Moreover, applicability deep learning is highlighted for development basis big data. These provide insight into interindividual factors enhance discovery precision medicine.

Language: Английский

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Precision and Accuracy of Single-Cell/Nuclei RNA Sequencing Data

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

Published: April 15, 2024

Abstract Single-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue the quality of sc/snRNA-Seq data that would impact reliability downstream analyses. Here we evaluated precision and accuracy 18 datasets. The was assessed on from human brain studies with a total 3,483,905 cells 297 individuals, by utilizing technical replicates. sample-matched scRNA-Seq pooled-cell RNA-Seq cultured mononuclear phagocytes four species. results revealed low at single-cell level across all data. Cell number were highlighted as two key factors determining expression precision, accuracy, reproducibility differential analysis sc/snRNA-Seq. This study underscores necessity enough high-quality per cell type individual, preferably hundreds, to mitigate noise quantification.

Language: Английский

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Fine-mapping causal tissues and genes at disease-associated loci

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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A unified framework for cell-type-specific eQTL prioritization by integrating bulk and scRNA-seq data

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing

Nature Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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