GammaGateR: semi-automated marker gating for single-cell multiplexed imaging DOI Creative Commons
Jiangmei Xiong, Harsimran Kaur, Cody N. Heiser

et al.

Bioinformatics, Journal Year: 2024, Volume and Issue: 40(6)

Published: June 1, 2024

Abstract Motivation Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses revert to marker gating based on manual thresholding of raw data. Results To address the need evaluable semi-automated algorithm, we developed GammaGateR, R package interactive designed specifically segmented data from images. Based novel closed-form gamma mixture model, GammaGateR provides estimates marker-positive proportions soft clustering cells. The model incorporates user-specified constraints provide consistent but slide-specific fit. We compared against newest unsupervised approach annotating data, employing two colon datasets one ovarian cancer dataset showed produces highly similar results silver standard established through annotation. Furthermore, demonstrated its effectiveness identifying biological signals, achieved by mapping known interactions between CD68 MUC5AC cells accurately predicting survival patients using phenotype probabilities input machine learning methods. efficient tool improve replicability results, while reducing time segmentation. Availability implementation available at https://github.com/JiangmeiRubyXiong/GammaGateR.

Language: Английский

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

Citations

53
New clinical trial design in precision medicine: discovery, development and direction DOI Creative Commons
Xiao-Peng Duan,

Bao‐Dong Qin,

Xiao‐Dong Jiao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to underestimation significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials could provide optimal therapy customization specific biomarkers were developed including basket, umbrella, platform trial designs under master protocol framework. recent years, successive FDA approval indications based on biomarker-guided demonstrated these new clinical ushering tremendous opportunities. Despite rapid increase number current research understanding designs, as compared remains limited. The majority focuses methodologies, there is lack in-depth insight concerning underlying biological logic designs. Therefore, we this comprehensive review discovery development their perspective medicine. Meanwhile, discuss future directions potential design view “Precision Pro”, “Dynamic Precision”, “Intelligent Precision”. This would assist trial-related researchers enhance innovation feasibility by expounding logic, which be essential accelerate progression

Language: Английский

Citations

49
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics DOI
Gunsagar S. Gulati,

Jeremy Philip D’Silva,

Yunhe Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31

Published: Aug. 21, 2024

Language: Английский

Citations

31
A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer DOI Creative Commons
Amelia Acha‐Sagredo, Pietro Andrei, Kalum Clayton

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Advancing Cancer Interception DOI Open Access
Susan M. Domchek, Robert H. Vonderheide

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(4), P. 600 - 604

Published: April 4, 2024

Summary: Rapid advances in technology and therapeutics, along with better methods to discern who is at risk for cancer by genetic testing other means, has enabled the development of interception. Targeted therapies “immuno-interception” may eliminate premalignant lesions require clinical trial treatment paradigms altogether distinct from current approaches.

Language: Английский

Citations

11
Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn’s disease DOI Creative Commons
Jia Li, Alan J. Simmons,

Caroline V. Hawkins

et al.

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

Published: Aug. 22, 2024

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify distinct epithelial cell type in terminal ileum ascending colon (hereon as 'LND') high expression of LCN2, NOS2, DUOX2 genes related to antimicrobial response immunoregulation. LND cells, confirmed by in-situ RNA protein imaging, are rare non-IBD controls but expand active CD, actively interact specifically express IBD/CD susceptibility genes, suggesting possible function CD immunopathogenesis. Furthermore, discover early late subpopulations different origins developmental potential. A higher ratio late-to-early correlates better anti-TNF treatment. Our findings thus suggest potential pathogenic role for ileitis colitis. Here the authors use multimodal data characterize an population, termed 'LND' colon, interacting locally potentially contributing pathology.

Language: Английский

Citations

11
The Hallmarks of Precancer DOI Open Access
Mary M. Stangis, Zhengyi Chen, Jimin Min

et al.

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(4), P. 683 - 689

Published: April 4, 2024

Summary: Research on precancers, as defined at-risk tissues and early lesions, is of high significance given the effectiveness intervention. We discuss need for risk stratification to prevent overtreatment, an emphasis role genetic epigenetic aging when considering risk, importance integrating macroenvironmental factors with molecules cells in lesions normal developing effective intervention health policy strategies.

Language: Английский

Citations

9
DDR1-targeted therapies: current limitations and future potential DOI

Donglin Wu,

Zihui Ding,

Tao Lü

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(5), P. 103975 - 103975

Published: April 4, 2024

Language: Английский

Citations

7
Seq-Scope Protocol: Repurposing Illumina Sequencing Flow Cells for High-Resolution Spatial Transcriptomics DOI Creative Commons
Yongsung Kim, Weiqiu Cheng, Chun‐Seok Cho

et al.

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

Published: April 1, 2024

ABSTRACT Spatial transcriptomics (ST) technologies represent a significant advance in gene expression studies, aiming to profile the entire transcriptome from single histological slide. These techniques are designed overcome constraints faced by traditional methods such as immunostaining and RNA situ hybridization, which capable of analyzing only few target genes simultaneously. However, application ST histopathological analysis is also limited several factors, including low resolution, range genes, scalability issues, high cost, need for sophisticated equipment complex methodologies. Seq-Scope—a recently developed novel technology—repurposes Illumina sequencing platform high-resolution, high-content spatial analysis, thereby overcoming these limitations. Here we provide detailed step-by-step protocol implement Seq-Scope with an NovaSeq 6000 flow cell that allows profiling multiple tissue sections area 7 mm × or larger. In addition detailing how prepare frozen section both imaging library preparation, comprehensive instructions streamlined computational pipeline integrate transcriptomic data high-resolution analysis. This includes use conventional software tools well our segmentation-free method at submicrometer resolution. Given its adaptability across various biological tissues, establishes itself invaluable tool researchers molecular biology histology. KEY POINTS The outlines repurposing array, enabling generation datasets. introduces produces digital matrix suitable single-cell methods. capture histology images same subjected users precisely align dataset image using fiducial marks engraved on surface. Leveraging commonly available equipment, offers ultra-high resolution pipeline, rapid turnaround, cost efficiency, versatility.

Language: Английский

Citations

5
Emerging strategies to investigate the biology of early cancer DOI
Ran Zhou, Xiwen Tang, Yuan Wang

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(12), P. 850 - 866

Published: Oct. 21, 2024

Language: Английский

Citations

5