Applications of deep learning in understanding gene regulation DOI Creative Commons
Zhongxiao Li,

Elva Gao,

Juexiao Zhou

et al.

Cell Reports Methods, Journal Year: 2023, Volume and Issue: 3(1), P. 100384 - 100384

Published: Jan. 1, 2023

Gene regulation is a central topic in cell biology. Advances omics technologies and the accumulation of data have provided better opportunities for gene studies than ever before. For this reason deep learning, as data-driven predictive modeling approach, has been successfully applied to field during past decade. In article, we aim give brief yet comprehensive overview representative deep-learning methods regulation. Specifically, discuss compare design principles datasets used by each method, creating reference researchers who wish replicate or improve existing methods. We also common problems approaches prospectively introduce emerging paradigms that will potentially alleviate them. hope article provide rich up-to-date resource shed light on future research directions area.

Language: Английский

Applications of single-cell sequencing in cancer research: progress and perspectives DOI Creative Commons

Yalan Lei,

Rong Tang, Jin Xu

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: June 9, 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics is a powerful tool to decipher the cellular molecular landscape at single-cell resolution, unlike bulk which provides averaged data. The use of sequencing in cancer research has revolutionized our understanding biological characteristics dynamics within lesions. In this review, we summarize emerging technologies recent progress obtained by information related landscapes malignant cells immune cells, tumor heterogeneity, circulating underlying mechanisms behaviors. Overall, prospects facilitating diagnosis, targeted therapy prognostic prediction among spectrum tumors are bright. near future, advances will undoubtedly improve highlight potential precise therapeutic targets for patients.

Language: Английский

Citations

356

SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks DOI Creative Commons
Carmen Bravo González‐Blas, Seppe De Winter, Gert Hulselmans

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(9), P. 1355 - 1367

Published: July 13, 2023

Abstract Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven regulatory networks (GRNs). Here we present a method for the inference GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TFs) links these target genes. To improve both recall precision TF identification, curated clustered motif collection more than 30,000 motifs. We benchmarked on diverse datasets from different species, including human peripheral blood mononuclear cells, ENCODE cell lines, melanoma states Drosophila retinal development. Next, exploit predictions study conserved TFs, GRNs between mouse types cerebral cortex. Finally, use dynamics regulation differentiation trajectories effect perturbations state. is available at scenicplus.readthedocs.io .

Language: Английский

Citations

284

Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface DOI Creative Commons
Miranda V. Hunter, Reuben Moncada, Joshua M. Weiss

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 1, 2021

Abstract During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq characterize tumor-microenvironment interactions at the boundary. Using a zebrafish model of melanoma, identify distinct “interface” state where contacts neighboring tissues. This interface composed specialized microenvironment that upregulate common set cilia genes, proteins are enriched only microenvironment. Cilia gene expression regulated by ETS-family transcription factors, which normally act suppress genes outside interface. A cilia-enriched conserved in human patient samples, suggesting feature melanoma. Our results demonstrate power transcriptomics uncovering mechanisms allow

Language: Английский

Citations

188

A cellular hierarchy in melanoma uncouples growth and metastasis DOI
Panagiotis Karras, Ignacio Bordeu, Joanna Poźniak

et al.

Nature, Journal Year: 2022, Volume and Issue: 610(7930), P. 190 - 198

Published: Sept. 21, 2022

Language: Английский

Citations

153

Cancer cell plasticity during tumor progression, metastasis and response to therapy DOI
Andrea Pérez-González, Kevin Bévant, Cédric Blanpain

et al.

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(8), P. 1063 - 1082

Published: Aug. 3, 2023

Language: Английский

Citations

143

Global computational alignment of tumor and cell line transcriptional profiles DOI Creative Commons

Allison Warren,

Yejia Chen,

Andrew Jones

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 4, 2021

Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Direct comparisons of and cell line transcriptional profiles complicated by several factors, including the variable presence normal cells in We thus develop an unsupervised alignment method (Celligner) apply to integrate large-scale RNA-Seq datasets. Although our aligns majority with samples same type, also reveals large differences similarity across lines. Using this approach, we identify hundred from diverse lineages that present a more mesenchymal undifferentiated state exhibit distinct chemical genetic dependencies. Celligner could be used guide selection closely resemble tumors improve clinical translation insights gained

Language: Английский

Citations

114

The journey from melanocytes to melanoma DOI
Patricia P. Centeno, Valeria Pavet, Richard Marais

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(6), P. 372 - 390

Published: April 24, 2023

Language: Английский

Citations

85

Single-cell technologies: From research to application DOI
Lu Wen, Guoqiang Li, Tao Huang

et al.

The Innovation, Journal Year: 2022, Volume and Issue: 3(6), P. 100342 - 100342

Published: Oct. 18, 2022

Language: Английский

Citations

84

EMT/MET plasticity in cancer and Go-or-Grow decisions in quiescence: the two sides of the same coin? DOI Creative Commons
Azamat Akhmetkaliyev,

Noura Alibrahim,

Darya Shafiee

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: May 31, 2023

Epithelial mesenchymal transition (EMT) and epithelial (MET) are genetic determinants of cellular plasticity. These programs operate in physiological (embryonic development, wound healing) pathological (organ fibrosis, cancer) conditions. In cancer, EMT MET interfere with various signalling pathways at different levels. This results gross alterations the gene expression programs, which affect most, if not all hallmarks such as response to proliferative death-inducing signals, tumorigenicity, cell stemness. cancer cells involves large scale reorganisation cytoskeleton, loss integrity, gain traits, type migration. this regard, EMT/MET plasticity is highly relevant Go-or-Grow concept, postulates dichotomous relationship between motility proliferation. The decisions critically important processes takes central stage, mobilisation stem during healing, relapse, metastasis. Here we outline maintenance quiescence metastatic niches, focusing on implication regulatory networks switches. particular, discuss analogy residing hybrid quasi-mesenchymal states GAlert, an intermediate phase allowing quiescent enter cycle rapidly.

Language: Английский

Citations

72

A TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma DOI Creative Commons
Joanna Poźniak, Dennis Pedri, Ewout Landeloos

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(1), P. 166 - 183.e25

Published: Jan. 1, 2024

To better understand intrinsic resistance to immune checkpoint blockade (ICB), we established a comprehensive view of the cellular architecture treatment-naive melanoma ecosystem and studied its evolution under ICB. Using single-cell, spatial multi-omics, showed that tumor microenvironment promotes emergence complex transcriptomic landscape. Melanoma cells harboring mesenchymal-like (MES) state, population known confer targeted therapy, were significantly enriched in early on-treatment biopsies from non-responders TCF4 serves as hub this landscape by being master regulator MES signature suppressor melanocytic antigen presentation transcriptional programs. Targeting genetically or pharmacologically, using bromodomain inhibitor, increased immunogenicity sensitivity ICB therapy. We thereby uncovered TCF4-dependent regulatory network orchestrates multiple programs contributes both therapy melanoma.

Language: Английский

Citations

69