Current sequence-based models capture gene expression determinants in promoters but mostly ignore distal enhancers DOI Creative Commons
Alexander Karollus, Thomas Mauermeier, Julien Gagneur

et al.

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: March 27, 2023

Abstract Background The largest sequence-based models of transcription control to date are obtained by predicting genome-wide gene regulatory assays across the human genome. This setting is fundamentally correlative, as those exposed during training solely sequence variation between genes that arose through evolution, questioning extent which capture genuine causal signals. Results Here we confront predictions state-of-the-art regulation against data from two large-scale observational studies and five deep perturbation assays. most advanced these models, Enformer, large, captures determinants promoters. However, fail effects enhancers on expression, notably in medium long distances particularly for highly expressed More generally, predicted impact distal elements expression small ability correctly integrate long-range information significantly more limited than receptive fields suggest. likely caused escalating class imbalance actual candidate distance increases. Conclusions Our results suggest have point silico study promoter regions variants can provide meaningful insights practical guidance how use them. Moreover, foresee it will require new kinds train accurately accounting elements.

Language: Английский

Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia DOI Creative Commons
Ugomma C. Eze, Aparna Bhaduri, Maximilian Haeussler

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(4), P. 584 - 594

Published: March 15, 2021

Abstract The human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium gives rise to radial glia, the neural stem cells of cortex. To characterize earliest stages brain development, we performed single-cell RNA-sequencing across regions developing brain, including telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal suggesting more heterogeneity than previously described, a highly prevalent mesenchymal-like population disappears once neurogenesis begins. Comparison mouse at corresponding identifies two clusters are enriched in early cortical development. also find organoid systems display low fidelity neuroepithelial glia types, but improve as progresses. Overall, provide comprehensive molecular spatial atlas

Language: Английский

Citations

346
Developmental dynamics of lncRNAs across mammalian organs and species DOI
Ioannis Sarropoulos,

Ray M. Marín,

Margarida Cardoso-Moreira

et al.

Nature, Journal Year: 2019, Volume and Issue: 571(7766), P. 510 - 514

Published: June 26, 2019

Language: Английский

Citations

278
Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors DOI
Johanna Theruvath, Elena Sotillo, Christopher Mount

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(5), P. 712 - 719

Published: April 27, 2020

Language: Английский

Citations

240
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells DOI Creative Commons
Daniel Franjic, Mario Škarica, Shaojie Ma

et al.

Neuron, Journal Year: 2021, Volume and Issue: 110(3), P. 452 - 469.e14

Published: Nov. 18, 2021

The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate potential cellular diversity, we profiled single-nucleus transcriptomes five subregions humans, macaques, pigs. Integrated cross-species analysis revealed robust transcriptomic histologic signatures of neurogenesis the adult mouse, pig, macaque but not humans. Doublecortin (DCX), a widely accepted marker newly generated granule cells, was detected diverse human neurons, it did define immature neuron populations. explore species differences diversity implications for disease, characterized subregion-specific, transcriptomically defined cell types transitional changes from three-layered archicortex six-layered neocortex. Notably, METTL7B subregion-specific excitatory neurons astrocytes primates, associated with endoplasmic reticulum lipid droplet proteins, including disease-related proteins. This resource reveals cell-type- species-specific properties shaping function.

Language: Английский

Citations

233
ROS1-dependent cancers — biology, diagnostics and therapeutics DOI
Alexander Drilon, Chelsea Jenkins, Sudarshan R. Iyer

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 18(1), P. 35 - 55

Published: Aug. 5, 2020

Language: Английский

Citations

212
A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes DOI Creative Commons
Razan E. Ahmed, Tatsuya Anzai, Nawin Chanthra

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: March 19, 2020

Cardiovascular diseases are the leading cause of death worldwide. Therefore, discovery induced pluripotent stem cells (iPSCs) and subsequent generation human cell-derived cardiomyocytes (hiPSC-CMs) was a pivotal point in regenerative medicine cardiovascular research. They constituted an appealing tool for replacing dead dysfunctional cardiac tissue, screening drugs toxins, studying inherited diseases. The problem is that these remain largely immature, order to utilize them, they must reach functional degree maturity. To attempt mimic

Language: Английский

Citations

200
Gene Set Analysis: Challenges, Opportunities, and Future Research DOI Creative Commons
Farhad Maleki, Katie Ovens, Daniel J. Hogan

et al.

Frontiers in Genetics, Journal Year: 2020, Volume and Issue: 11

Published: June 30, 2020

Gene set analysis methods are widely used to provide insight into high-throughput gene expression data. There many available. These rely on various assumptions and have different requirements, strengths weaknesses. In this paper, we classify based their components, describe the underlying requirements for each class, directions future research in developing evaluating methods.

Language: Английский

Citations

177
Human brain organogenesis: Toward a cellular understanding of development and disease DOI Creative Commons

Kevin W. Kelley,

Sergiu P. Paşca

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 42 - 61

Published: Nov. 11, 2021

Language: Английский

Citations

176
Transcriptome and translatome co-evolution in mammals DOI

Zhongyi Wang,

Evgeny Leushkin, Angélica Liechti

et al.

Nature, Journal Year: 2020, Volume and Issue: 588(7839), P. 642 - 647

Published: Nov. 11, 2020

Language: Английский

Citations

170
AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations DOI Creative Commons

Wen‐Kang Shen,

Si‐Yi Chen,

Zi-Quan Gan

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D39 - D45

Published: Oct. 5, 2022

Abstract Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up new data provide a more comprehensive resource for TF research, we updated the Animal Factor Database (AnimalTFDB) version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) up-to-date functions. We refined family rules prediction pipeline predict TFs genome-wide protein from Ensembl. As result, predicted 274 633 genes 150 726 transcription cofactor AnimalTFDB 183 animal genomes, which 86 species than 3.0. Besides double volume, also added following annotations functions database: (i) variations (including mutations) on various human cancers other diseases; (ii) post-translational modification sites phosphorylation, acetylation, methylation ubiquitination sites) 8 species; (iii) regulation autophagy; (iv) annotation 38 (v) exact batch search allow users flexibly. is useful studying regulation, contains classification cofactors.

Language: Английский

Citations

160