HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics

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

Published: July 7, 2024

Abstract Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, distribution-free, test-based method fast accurately identifying large-scale transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher $${F}_{1}$$ F 1 scores (average Score=0.948), improved computational efficiency, scalability, reduced false positives (FPs). Through analysis twelve real datasets from various technologies, identifies greater number biologically significant SVGs AUC = 0.792) than other comparative without prespecifying patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor domains characterized unique expression patterns, spatial-temporal locations, biological functions human colorectal cancer data, unraveling complexity tumors.

Language: Английский

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Omics Studies of Tumor Cells under Microgravity Conditions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 926 - 926

Published: Jan. 11, 2024

Cancer is defined as a group of diseases characterized by abnormal cell growth, expansion, and progression with metastasis. Various signaling pathways are involved in its development. Malignant tumors exhibit high morbidity mortality. research increased our knowledge about some the underlying mechanisms, but to this day, understanding disease unclear. High throughput omics technology bioinformatics were successful detecting unknown cancer mechanisms. However, novel groundbreaking ideas necessary. A stay orbit causes biochemical molecular biological changes human cells which first, above all, due microgravity (µg). The µg-environment provides conditions that not reachable on Earth, allow researchers focus controlling growth space already demonstrated how cell-exposure µg influenced several processes being cancer. This approach has potential fight develop future strategies. Space been shown impact like proliferation, apoptosis, survival, adhesion, migration, cytoskeleton, extracellular matrix, focal factors, among others. concise review focuses publications related genetic, transcriptional, epigenetic, proteomic, metabolomic studies tumor exposed real or simulated using simulation devices. We discuss all investigating different types from brain hematological system, sarcomas, well thyroid, prostate, breast, gynecologic, gastrointestinal, lung cancers, order gain new innovative for basic biology

Language: Английский

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Tolerogenic Nano-/Microparticle Vaccines for Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Autoimmune diseases, allergies, transplant rejections, generation of antidrug antibodies, and chronic inflammatory diseases have impacted a large group people across the globe. Conventional treatments therapies often use systemic or broad immunosuppression with serious efficacy safety issues. Tolerogenic vaccines represent concept that has been extended from their traditional immune-modulating function to induction antigen-specific tolerance through regulatory T cells. Without impairing immune homeostasis, tolerogenic dampen inflammation induce regulation. However, achieving desired potency as preventive therapeutic modalities calls for precise manipulation microenvironment control over responses against autoantigens, allergens, and/or alloantigens. Engineered nano-/microparticles possess desirable design features can bolster targeted regulation enhance tolerance. Thus, particle-based hold great promise in clinical translation future treatment aforementioned disorders. In this review, we highlight main strategies employ particles exciting vaccines, focus on particles' role facilitating We describe particle facilitate usage discuss challenges opportunities designing next-generation robust promote immunotherapy.

Language: Английский

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Spatially Resolved Single-Cell Omics: Methods, Challenges, and Future Perspectives

Annual Review of Biomedical Data Science, Journal Year: 2024, Volume and Issue: 7(1), P. 131 - 153

Published: May 20, 2024

Overlaying omics data onto spatial biological dimensions has been a promising technology to provide high-resolution insights into the interactome and cellular heterogeneity relative organization of molecular microenvironment tissue samples in normal disease states. Spatial can be categorized three major modalities: (a) next-generation sequencing–based assays, (b) imaging-based spatially resolved transcriptomics approaches including situ hybridization/in sequencing, (c) proteomics. These modalities allow assessment transcripts proteins at level, generating large computationally challenging datasets. The lack standardized computational pipelines analyze integrate these nonuniform structured made it necessary apply artificial intelligence machine learning strategies best visualize translate their complexity. In this review, we summarize currently available techniques strategies, highlight advantages limitations, discuss future prospects scientific field.

Language: Английский

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Spatial oncology: Translating contextual biology to the clinic

Cancer Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Lactate as Key Metabolite in Prostate Cancer Progression: What Are the Clinical Implications?

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3473 - 3473

Published: July 3, 2023

Advanced prostate cancer represents the fifth leading cause of death in men worldwide. Although androgen-receptor signaling is major driver disease, evidence accumulating that disease progression supported by substantial metabolic changes. Alterations de novo lipogenesis and fatty acid catabolism are consistently reported during development association with signaling. Therefore, term "lipogenic phenotype" frequently used to describe complex rewiring occurs cancer. However, a new scenario has emerged which lactate may play role. oncogenes/tumor suppressors, androgen signaling, hypoxic conditions, cells tumor microenvironment can promote aerobic glycolysis release microenvironment, favoring immune evasion metastasis. As composed metabolically heterogenous cells, glycolytic or cancer-associated fibroblasts also secrete create "symbiotic" interactions oxidative via shuttling sustain progression. Here, we discuss multifaceted role progression, taking into account influence systemic gut microbiota. We call special attention clinical opportunities imaging accumulation for patient stratification targeting metabolism.

Language: Английский

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Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 27, 2024

Abstract Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens encompasses both spatial temporal dimensions. Conventional omics methodologies, such as genomics transcriptomics, been instrumental in identifying critical facets of aging regeneration. However, methods are somewhat limited, constrained by their resolution lack capacity dynamically tissue alterations. The advent emerging spatiotemporal multi-omics approaches, encompassing proteomics, metabolomics, epigenomics, furnishes comprehensive insights into intricate dynamics. These sophisticated techniques facilitate accurate delineation patterns across an array cells, tissues, organs, thereby offering in-depth understanding fundamental mechanisms at play. This review meticulously examines significance realms research. It underscores how methodologies augment our comprehension dynamics, cellular interactions, signaling pathways. Initially, delineates foundational principles underpinning methods, followed evaluation recent applications within field. ultimately concludes addressing prevailing challenges projecting future advancements Indubitably, deciphering complexities inherent regeneration, thus charting course toward potential therapeutic innovations.

Language: Английский

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Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis

Immunological Reviews, Journal Year: 2023, Volume and Issue: 319(1), P. 100 - 127

Published: Aug. 8, 2023

Cancers are genetically driven, rogue tissues which generate dysfunctional, obdurate organs by hijacking normal, homeostatic programs. Apoptosis is an evolutionarily conserved regulated cell death program and a profoundly important mechanism that common (alongside tumor proliferation) in actively growing cancers, as well tumors responding to cytotoxic anti-cancer therapies. Although known for its cell-autonomous tumor-suppressive qualities, apoptosis harbors pro-oncogenic properties deployed through non-cell-autonomous mechanisms generally remain poorly defined. Here, the roles of biology reviewed, with particular focus on secreted fragmentation products apoptotic cells their effects tumor-associated macrophages, key supportive aberrant homeostasis microenvironment. Historical aspects loss growth kinetics considered impact (and potential impact) apoptotic-cell clearance (efferocytosis) released soluble extracellular vesicle-associated factors discussed from perspectives inflammation, tissue repair, regeneration An "apoptosis-centric" view proposed dying provide platform intricate intercellular communication networks cancers. The perspective has implications future research improving cancer diagnosis therapy.

Language: Английский

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Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Nov. 8, 2023

Abstract Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as benefit only available for a fraction patients. A lack understanding CAR-T behaviors vivo at the single-cell level impedes their more extensive application practice. Mounting evidence suggests that sequencing techniques can help perfect design, guide gene-based T modification, and optimize manufacturing conditions, all them are essential long-term immunosurveillance favorable outcomes. The information generated by employing these methods also potentially informs our numerous complex factors dictate therapeutic efficacy toxicities. In this review, we discuss reasons why immunotherapy fails practice what field has learned since milestone technologies. We further outline recent advances analyses immunotherapy. Specifically, provide an overview studies focusing on target antigens, CAR-transgene integration, preclinical research applications, then how it will affect future therapy.

Language: Английский

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Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 30, 2024

Abstract Leukemias are refractory hematological malignancies, characterized by marked intrinsic heterogeneity which poses significant obstacles to effective treatment. However, traditional bulk sequencing techniques have not been able effectively unravel the among individual tumor cells. With emergence of single-cell technology, it has bestowed upon us an unprecedented resolution comprehend mechanisms underlying leukemogenesis and drug resistance across various levels, including genome, epigenome, transcriptome proteome. Here, we provide overview currently prevalent technologies a detailed summary studies conducted on leukemia, with specific focus four key aspects: (1) leukemia’s clonal architecture, (2) frameworks determine leukemia subtypes, (3) microenvironment (TME) (4) drug-resistant leukemia. This review provides comprehensive current highlights markers that show promising clinical implications for diagnosis treatment

Language: Английский

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