Brain Chimeroids reveal individual susceptibility to neurotoxic triggers

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 142 - 149

Published: June 26, 2024

Language: Английский

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Toward a foundation model of causal cell and tissue biology with a Perturbation Cell and Tissue Atlas

Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4520 - 4545

Published: Aug. 1, 2024

Language: Английский

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A Decade in a Systematic Review: The Evolution and Impact of Cell Painting

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

Published: May 7, 2024

ABSTRACT High-content image-based assays have fueled significant discoveries in the life sciences past decade (2013-2023), including novel insights into disease etiology, mechanism of action, new therapeutics, and toxicology predictions. Here, we systematically review substantial methodological advancements applications Cell Painting. Advancements include improvements Painting protocol, assay adaptations for different types perturbations applications, improved methodologies feature extraction, quality control, batch effect correction. Moreover, machine learning methods recently surpassed classical approaches their ability to extract biologically useful information from images. data been used alone or combination with other - omics decipher action a compound, its toxicity profile, many biological effects. Overall, key advances expanded Painting’s capture cellular responses various perturbations. Future will likely lie advancing computational experimental techniques, developing publicly available datasets, integrating them high-content types.

Language: Английский

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The genetic basis of autoimmunity seen through the lens of T cell functional traits

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 8, 2024

Autoimmune disease heritability is enriched in T cell-specific regulatory regions of the genome. Modern-day cell datasets now enable association studies between single nucleotide polymorphisms (SNPs) and a myriad molecular phenotypes, including chromatin accessibility, gene expression, transcriptional programs, antigen receptor (TCR) amino acid usage, state abundances. Such have identified hundreds quantitative trait loci (QTLs) cells that colocalize with genetic risk for autoimmune disease. The key challenge facing immunologists today lies synthesizing these results toward unified understanding cell: which genes, states, antigens drive tissue destruction?

Language: Английский

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A systematic evaluation of computational methods for cell segmentation

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(5)

Published: July 25, 2024

Cell segmentation is a fundamental task in analyzing biomedical images. Many computational methods have been developed for cell and instance segmentation, but their performances are not well understood various scenarios. We systematically evaluated the performance of 18 to perform nuclei whole using light microscopy fluorescence staining found that general-purpose incorporating attention mechanism exhibit best overall performance. identified factors influencing performances, including image channels, choice training data, morphology, generalizability across modalities. also provide guidelines choosing optimal real application Seggal, an online resource downloading models already pre-trained with tissue types, substantially reducing time effort models.

Language: Английский

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Microfluidics for morpholomics and spatial omics applications

Lab on a Chip, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Created in BioRender. Menon, N. (2025). https://www.BioRender.com/l48m487.

Language: Английский

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Unbiased identification of cell identity in dense mixed neural cultures

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 17, 2025

Induced pluripotent stem cell (iPSC) technology is revolutionizing biology. However, the variability between individual iPSC lines and lack of efficient to comprehensively characterize iPSC-derived types hinder its adoption in routine preclinical screening settings. To facilitate validation culture composition, we have implemented an imaging assay based on painting convolutional neural networks recognize dense mixed cultures with high fidelity. We benchmarked our approach using pure neuroblastoma astrocytoma attained a classification accuracy above 96%. Through iterative data erosion, found that inputs containing nuclear region interest close environment, allow achieving equally as whole for semi-confluent preserved prediction even very cultures. then applied this regionally restricted profiling evaluate differentiation status cultures, by determining ratio postmitotic neurons progenitors. cell-based significantly outperformed which population-level time was used criterion (96% vs 86%, respectively). In neuronal microglia could be unequivocally discriminated from neurons, regardless their reactivity state, tiered strategy allowed further distinguishing activated non-activated states, albeit lower accuracy. Thus, morphological single-cell provides means quantify composition complex holds promise use quality control models.

Language: Английский

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Effectively Guiding Cell Elongation and Alignment by Constructing Micro/Nano Hierarchical Patterned Titania on Titanium Substrate

Biotechnology and Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT Based on the innate sensitivity of cell to substrate topographical cues, modulating cell‐directed growth behavior is crucial for promoting tissue repair and reconstruction. Although photolithography technology has been extensively employed fabricate a variety anisotropic patterned structures guide growth, it remains great challenge design high‐resolution micro/nano hierarchical directly onto medical titanium (Ti)‐based implants. Herein, we present rapid, reliable reproducible approach combining hydrothermal construct structure including micro‐strips porous composed TiO 2 nanotubes features. In vitro biological physicochemical analyses revealed that not only efficiently facilitate localization adsorption BSA molecules, but also enhances control behavior. The synergistic effect between physical limitation organizing cellular cytoskeleton at micropattern focal adhesion sits nanoscale can effectively cells maintain stable elongation alignment, even large micro‐stripe width 100 μm. This study presents promising strategy precisely multi‐level Ti using biomaterials with excellent biocompatibility. These functional hybrid micropatterns offer powerful platform regulating bioreagent behaviors in various applications engineering, regenerative medicine, drug screening, biosensors.

Language: Английский

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Network-aware self-supervised learning enables high-content phenotypic screening for genetic modifiers of neuronal activity dynamics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract High-throughput phenotypic screening has historically relied on manually selected features, limiting our ability to capture complex cellular processes, particularly neuronal activity dynamics. While recent advances in self-supervised learning have revolutionized the study morphology and transcriptomics, dynamic processes remained challenging phenotypically profile. To address this limitation, we developed Plexus, a novel model specifically designed quantify network-level Unlike existing phenotyping tools that focus static readouts, Plexus leverages cell encoding method, which enables it efficiently encode data into rich representational embeddings. In turn, achieves state of art performance detecting changes activity. We validated using comprehensive GCaMP6m simulation framework demonstrated its enhanced classify distinct phenotypes compared traditional signal-processing approaches. enable practical application, integrated with scalable experimental system utilizing human iPSC-derived neurons equipped calcium indicator CRISPR interference machinery. This platform successfully identified nearly twice as many response genetic perturbations conventional methods, 52-gene CRISPRi screen across multiple iPSC lines. Using framework, potential modifiers aberrant frontotemporal dementia, illustrating utility for understanding neurological disorders.

Language: Английский

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Evaluating feature extraction in ovarian cancer cell line co-cultures using deep neural networks

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 25, 2025

Abstract Single-cell image analysis is crucial for studying drug effects on cellular morphology and phenotypic changes. Most studies focus single cell types, overlooking the complexity of interactions. Here, we establish an pipeline to extract features cancer cells cultured with fibroblasts. Using high-content imaging, analyze oncology library across five fibroblast line co-culture combinations, generating 61,440 images ∼170 million single-cell objects. Traditional phenotyping CellProfiler achieves average enrichment score 62.6% mechanisms action, while pre-trained neural networks (EfficientNetB0 MobileNetV2) reach 61.0% 62.0%, respectively. Variability in scores may reflect use multiple concentrations since not all induce significant morphological changes, as well genetic context treatment. Our study highlights nuanced drug-induced variations underscores heterogeneity ovarian lines their response complex environments.

Language: Английский

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