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Article ; Online: A continuous model of early mammalian development.

Qiu, Chengxiang / Shendure, Jay

2021 Volume 593, Issue 7858, Page(s) 200–201

MeSH term(s)	Animals ; Embryo, Mammalian ; Mammals
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	News ; Comment
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/d41586-021-01153-1
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Article: Multi-condition and multi-modal temporal profile inference during mouse embryonic development.

Zhang, Ran / Qiu, Chengxiang / Filippova, Gala / Li, Gang / Shendure, Jay / Vert, Jean-Philippe / Deng, Xinxian / Disteche, Christine / Noble, William Stafford

bioRxiv : the preprint server for biology

2024

Abstract: The emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of ... ...

Abstract	The emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of a particular cell. Furthermore, single-cell profiles can be collected at mismatched time points across different conditions (e.g., sex, batch, disease) and data modalities (e.g., scRNA-seq, scATAC-seq), which makes modeling challenging. Here we propose a joint modeling framework, Sunbear, for integrating multi-condition and multi-modal single-cell profiles across time. Sunbear can be used to impute single-cell temporal profile changes, align multi-dataset and multi-modal profiles across time, and extrapolate single-cell profiles in a missing modality. We applied Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multi-modal profiles are unavailable. Sunbear thus enables the projection of single-cell time-series snapshots to multi-modal and multi-condition views of cellular trajectories.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.03.583179
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Article: Induction and

Hamazaki, Nobuhiko / Yang, Wei / Kubo, Connor / Qiu, Chengxiang / Martin, Beth K / Garge, Riddhiman K / Regalado, Samuel G / Nichols, Eva / Lee, Choli / Daza, Riza M / Srivatsan, Sanjay / Shendure, Jay

bioRxiv : the preprint server for biology

2024

Abstract: Embryonic organoids are emerging as powerful models for studying early mammalian development. For example, stem cell-derived 'gastruloids' form elongating structures containing all three germ ... ...

Abstract	Embryonic organoids are emerging as powerful models for studying early mammalian development. For example, stem cell-derived 'gastruloids' form elongating structures containing all three germ layers
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.10.579769
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genome-wide association studies identify the role of caspase-9 in kidney disease.

Doke, Tomohito / Huang, Shizheng / Qiu, Chengxiang / Sheng, Xin / Seasock, Matthew / Liu, Hongbo / Ma, Ziyuan / Palmer, Matthew / Susztak, Katalin

Science advances

2021 Volume 7, Issue 45, Page(s) eabi8051

Abstract: Genome-wide association studies (GWAS) have identified hundreds of genetic risk regions for kidney dysfunction [estimated glomerular filtration rate (eGFR)]; however, the causal genes, cell types, and pathways are poorly understood. Integration of GWAS ... ...

Abstract	Genome-wide association studies (GWAS) have identified hundreds of genetic risk regions for kidney dysfunction [estimated glomerular filtration rate (eGFR)]; however, the causal genes, cell types, and pathways are poorly understood. Integration of GWAS and human kidney expression of quantitative trait analysis using Bayesian colocations, transcriptome-wide association studies, and summary-based Mendelian randomization studies prioritized caspase-9 (CASP9) as a kidney disease risk gene. Human kidney single-cell epigenetic and immunostaining studies indicated kidney tubule cells as a disease-causing cell type. Mice with genetic deletion or pharmacological inhibition of CASP9 showed lower apoptosis while having improved mitophagy, resulting in dampened activation of cytosolic nucleotide sensing pathways (cGAS-STING), reduction of inflammation, and protection from acute kidney disease or renal fibrosis. In summary, here, we prioritized CASP9 as an eGFR GWAS target gene and demonstrated the causal role of CASP9 in kidney disease development via improving mitophagy and lowering inflammation and apoptosis.
Language	English
Publishing date	2021-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abi8051
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Large-Scale Analysis of the Relationship of Synonymous SNPs Changing MicroRNA Regulation with Functionality and Disease.

Wang, Yuchen / Qiu, Chengxiang / Cui, Qinghua

International journal of molecular sciences

2015 Volume 16, Issue 10, Page(s) 23545–23555

Abstract: Historically, owing to not changing amino acid composition of protein sequences, synonymous mutations are commonly assumed to be neutral during evolution and therefore have no effect on the phenotype and disease. Here, based on observations from large- ... ...

Abstract	Historically, owing to not changing amino acid composition of protein sequences, synonymous mutations are commonly assumed to be neutral during evolution and therefore have no effect on the phenotype and disease. Here, based on observations from large-scale analysis of genomic data, we predicted the putative synonymous SNPs that could result in functional consequences and disease risk through changing the microRNA-mediated gene regulation. We found that nearly half of the synonymous SNPs could affect protein expression by changing microRNA regulation in human genome and these SNPs significantly prefer to be associated with human diseases and traits. The synonymous SNPs changing microRNA-mediated gene regulation tend to be more under recent positive selection, prefer to affect gene expression, and implicate in human disease. We conclude that the miRNA-mediated regulation changes could be a potential mechanism for the contributions of synonymous SNPs to protein functions and disease risks.
MeSH term(s)	Gene Expression Regulation ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Haplotypes/genetics ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Models, Genetic ; Mutation ; Polymorphism, Single Nucleotide/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2015-09-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms161023545
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Article ; Online: Optimized single-nucleus transcriptional profiling by combinatorial indexing.

Martin, Beth K / Qiu, Chengxiang / Nichols, Eva / Phung, Melissa / Green-Gladden, Rula / Srivatsan, Sanjay / Blecher-Gonen, Ronnie / Beliveau, Brian J / Trapnell, Cole / Cao, Junyue / Shendure, Jay

Nature protocols

2022 Volume 18, Issue 1, Page(s) 188–207

Abstract: Single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) is a powerful method for recovering gene expression data from an exponentially scalable number of individual cells or nuclei. However, sci-RNA-seq is a complex protocol that has historically ...

Abstract	Single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) is a powerful method for recovering gene expression data from an exponentially scalable number of individual cells or nuclei. However, sci-RNA-seq is a complex protocol that has historically exhibited variable performance on different tissues, as well as lower sensitivity than alternative methods. Here, we report a simplified, optimized version of the sci-RNA-seq protocol with three rounds of split-pool indexing that is faster, more robust and more sensitive and has a higher yield than the original protocol, with reagent costs on the order of 1 cent per cell or less. The total hands-on time from nuclei isolation to final library preparation takes 2-3 d, depending on the number of samples sharing the experiment. The improvements also allow RNA profiling from tissues rich in RNases like older mouse embryos or adult tissues that were problematic for the original method. We showcase the optimized protocol via whole-organism analysis of an E16.5 mouse embryo, profiling ~380,000 nuclei in a single experiment. Finally, we introduce a 'Tiny-Sci' protocol for experiments in which input material is very limited.
MeSH term(s)	Animals ; Mice ; Gene Expression Profiling/methods ; RNA-Seq ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; RNA/genetics ; RNA/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2022-10-19
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-022-00752-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Drug-Path: a database for drug-induced pathways.

Zeng, Hui / Qiu, Chengxiang / Cui, Qinghua

Database : the journal of biological databases and curation

2015 Volume 2015, Page(s) bav061

Abstract: Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray ...

Abstract	Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches.
MeSH term(s)	Animals ; Databases, Genetic ; Gene Expression Regulation/drug effects ; Humans ; Pharmaceutical Preparations/metabolism ; Pharmacokinetics ; Programming Languages
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2015
Publishing country	England
Document type	Dataset ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/bav061
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: miR2Gene

Qiu Chengxiang / Wang Juan / Cui Qinghua

BMC Systems Biology, Vol 5, Iss Suppl 2, p S

pattern discovery of single gene, multiple genes, and pathways by enrichment analysis of their microRNA regulators

2011 Volume 9

Abstract: Abstract Background In recent years, a number of tools have been developed to explore microRNAs (miRNAs) by analyzing their target genes. However, a reverse problem, that is, inferring patterns of protein-coding genes through their miRNA regulators, has ... ...

Abstract	Abstract Background In recent years, a number of tools have been developed to explore microRNAs (miRNAs) by analyzing their target genes. However, a reverse problem, that is, inferring patterns of protein-coding genes through their miRNA regulators, has not been explored. As various miRNA annotation data become available, exploring gene patterns by analyzing the prior knowledge of their miRNA regulators is becoming more feasible. Results In this study, we developed a tool, miR2Gene, for this purpose. Various sets of miRNAs, according to prior rules such as function, associated disease, tissue specificity, family, and cluster, were integrated with miR2Gene. For given genes, miR2Gene evaluates the enrichment of the predicted miRNAs that regulate them in each miRNA set. This tool can be used for single genes, multiple genes, and KEGG pathways. For the KEGG pathway, genes with enriched miRNA sets are highlighted according to various rules. We confirmed the usefulness of miR2Gene through case studies. Conclusions miR2Gene represents a novel and useful tool that integrates miRNA knowledge for protein-coding gene analysis. miR2Gene is freely available at http://cmbi.hsc.pku.edu.cn/mir2gene .
Keywords	Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2011-12-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systematic reconstruction of cellular trajectories across mouse embryogenesis.

Qiu, Chengxiang / Cao, Junyue / Martin, Beth K / Li, Tony / Welsh, Ian C / Srivatsan, Sanjay / Huang, Xingfan / Calderon, Diego / Noble, William Stafford / Disteche, Christine M / Murray, Stephen A / Spielmann, Malte / Moens, Cecilia B / Trapnell, Cole / Shendure, Jay

Nature genetics

2022 Volume 54, Issue 3, Page(s) 328–341

Abstract: Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells expressing a panoply of molecular programs. Although intensively studied, a ... ...

Abstract	Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells expressing a panoply of molecular programs. Although intensively studied, a comprehensive delineation of the major cellular trajectories that comprise mammalian development in vivo remains elusive. Here, we set out to integrate several single-cell RNA-sequencing (scRNA-seq) datasets that collectively span mouse gastrulation and organogenesis, supplemented with new profiling of ~150,000 nuclei from approximately embryonic day 8.5 (E8.5) embryos staged in one-somite increments. Overall, we define cell states at each of 19 successive stages spanning E3.5 to E13.5 and heuristically connect them to their pseudoancestors and pseudodescendants. Although constructed through automated procedures, the resulting directed acyclic graph (TOME (trajectories of mammalian embryogenesis)) is largely consistent with our contemporary understanding of mammalian development. We leverage TOME to systematically nominate transcription factors (TFs) as candidate regulators of each cell type's specification, as well as 'cell-type homologs' across vertebrate evolution.
MeSH term(s)	Animals ; Embryo, Mammalian ; Embryonic Development/genetics ; Gastrulation/genetics ; Mammals ; Mice ; Organogenesis
Language	English
Publishing date	2022-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-022-01018-x
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Article ; Online: Embryo model completes gastrulation to neurulation and organogenesis.

Amadei, Gianluca / Handford, Charlotte E / Qiu, Chengxiang / De Jonghe, Joachim / Greenfeld, Hannah / Tran, Martin / Martin, Beth K / Chen, Dong-Yuan / Aguilera-Castrejon, Alejandro / Hanna, Jacob H / Elowitz, Michael B / Hollfelder, Florian / Shendure, Jay / Glover, David M / Zernicka-Goetz, Magdalena

Nature

2022 Volume 610, Issue 7930, Page(s) 143–153

Abstract: Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in ... ...

Abstract	Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro
MeSH term(s)	Animals ; Cell Lineage ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryonic Stem Cells/cytology ; Endoderm/cytology ; Endoderm/embryology ; Gastrulation ; Heart/embryology ; Mesencephalon/embryology ; Mice ; Models, Biological ; Neural Tube/embryology ; Neurulation ; Organogenesis ; PAX6 Transcription Factor/deficiency ; PAX6 Transcription Factor/genetics ; Prosencephalon/embryology ; Somites/embryology
Chemical Substances	PAX6 Transcription Factor ; Pax6 protein, mouse
Language	English
Publishing date	2022-08-25
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05246-3
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Zs.MG 9: Show issues
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