Integrative analysis of bulk and single-cell RNA-seq data for cardiometabolic disease
Integrative analysis of bulk and single-cell RNA-seq data for cardiometabolic disease
批准号:
10448317
负责人:
Mingyao Li
金额:
$12.19万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-07-15 至 2024-06-30
关键词:
AbdomenAccountingAdipocytesAdipose tissueAllelic ImbalanceArchitectureAtherosclerosisBody mass indexBuffersCandidate Disease GeneCardiometabolic DiseaseCatalogsCellsCholesterolComplexComputer softwareDataData AnalysesData SetDiseaseElementsEndothelial CellsEtiologyFibroblastsFoundationsFunctional disorderFundingGene ExpressionGenesGeneticGenetic DiseasesGenetic TranscriptionGenomeGenotypeHeterogeneityHigh-Throughput RNA SequencingHumanImmuneKnowledgeLinkLipidsLocationLoose connective tissueMeasurableMetabolicMethodsMolecularMorbidity - disease rateMuscleMyocardial InfarctionNational Heart, Lung, and Blood InstituteNational Human Genome Research InstituteNeedle biopsy procedureNon-Insulin-Dependent Diabetes MellitusObesityPeripheralPrecision therapeuticsPublishingQuantitative Trait LociRegulatory ElementReportingResolutionRiskRoleSamplingSingle Nucleotide PolymorphismStatistical Data InterpretationStatistical MethodsStrokeSystemTestingTissuesTriglyceridesUntranslated RNAVariantWaist-Hip RatioWhole Bloodadiponectinbasecardiometabolic riskcell typeenergy balancegenetic associationgenetic variantgenome wide association studygenomic locushuman datainsightinterestlifestyle factorsmacrophagemortalitynovelopen sourcesingle-cell RNA sequencingstatisticsstem cellssubcutaneoustherapeutic targettraittranscriptometranscriptome sequencingtranscriptomics
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Cardiometabolic diseases (CMD), including obesity, type 2 diabetes, heart attack, stroke, and atherosclerosis,
are caused by the effects and complex interplay of genetic and lifestyle factors. In the past decade, there has
been a dramatic increase of CMD, which represents important causes of morbidity and mortality worldwide.
Therefore, there is a great interest to understand the etiology and pathophysiology of CMD. Recent genome-
wide association studies (GWAS) have provided increased insight into the genetic basis for CMD and related
traits. Although GWAS have identified strong and highly replicated association of genetic loci for CMD and their
related traits, GWAS findings can only suggest locations of associated variants and not directly link any one
gene within a region to disease. Since most GWAS-identified single nucleotide polymorphisms (SNPs) are
located in non-coding regions of the genome, their influence on disease is likely to be on modulating RNA
expression by acting as expression quantitative trait loci (eQTL). Excess adipose tissue, especially in central
abdominal depots, is associated with increased risk of CMD. Subcutaneous adipose tissue stores additional
lipids and acts as a buffering system for lipid energy balance, thus providing a protective role for CMD.
Previous eQTL studies in subcutaneous adipose tissue have implicated genes involved in obesity and
metabolic traits. However, the role of candidate genes identified in GWAS is still not yet clear because
published eQTL studies were based on bulk tissue gene expression in adipose. Adipose tissue is a loose
connective tissue that is composed mostly of adipocytes. In addition to adipocytes, adipose tissue also
contains adipocyte progenitor cells, endothelial cells, fibroblasts, and various immune cells such as
macrophages. The resulting heterogeneity between samples can confound the analysis of bulk tissue data. To
overcome these limitations, we propose to perform integrative secondary data analysis of publically available
bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data from human adipose. We will test
the hypothesis that measurable molecular deficits that include cell types and gene expression occur in adipose
for CMD. We will further integrate with publically available GWAS data on CMD to advance post-GWAS
interpretation of CMD genetic results. By detailed characterization of cell-type composition and cell-type-
specific gene expression changes in human adipose, our results will elucidate the functional roles of GWAS
findings that are still poorly understood and can power precision therapeutic targeting of CMD.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.
人颈动脉粥样硬化的高维单细胞多模态景观。
DOI:
10.1101/2023.07.13.23292633
发表时间:
2023
期刊:
medRxiv : the preprint server for health sciences
影响因子:
--
作者:
[Bashore,AlexanderC, Yan,Hanying, Xue,Chenyi, Zhu,LucieY, Kim,Eunyoung, Mawson,Thomas, Coronel,Johana, Chung,Allen, Ho,Sebastian, Ross,LeilaS, Kissner,Michael, Passegué,Emmanuelle, Bauer,RobertC, Maegdefessel,Lars, Li,Mingyao, Reilly,Mu]
通讯作者:
Reilly,Mu
Data Core
-
批准号:10806551
-
项目类别:
-
资助金额:$76.5万
-
财政年份:2023
-
负责人:Mingyao Li
-
依托单位:
Integrative analysis of spatial transcriptomics with histology images and single cells
-
批准号:10733815
-
项目类别:
-
资助金额:$54.66万
-
财政年份:2023
-
负责人:Mingyao Li
-
依托单位:
The Penn Human Precision Pain Center (HPPC): Discovery and Functional Evaluation of Human Primary Somatosensory Neuron Types at Normal and Chronic Pain Conditions
-
批准号:10806545
-
项目类别:
-
资助金额:$675.15万
-
财政年份:2023
-
负责人:Mingyao Li
-
依托单位:
Computational and functional strategies to decipher lncRNAs in human atherosclerosis
-
批准号:10347301
-
项目类别:
-
资助金额:$66.03万
-
财政年份:2020
-
负责人:Mingyao Li
-
依托单位:
Computational and functional strategies to decipher lncRNAs in human atherosclerosis
-
批准号:10557797
-
项目类别:
-
资助金额:$66.03万
-
财政年份:2020
-
负责人:Mingyao Li
-
依托单位:
Computational and functional strategies to decipher lncRNAs in human atherosclerosis
-
批准号:10091516
-
项目类别:
-
资助金额:$65.18万
-
财政年份:2020
-
负责人:Mingyao Li
-
依托单位:
Integrative analysis of bulk and single-cell RNA-seq data from human retina for age-related macular degeneration
-
批准号:10241966
-
项目类别:
-
资助金额:$23.97万
-
财政年份:2020
-
负责人:Mingyao Li
-
依托单位:
Single-Cell Transcriptomic Analysis of Human Retina
-
批准号:10159930
-
项目类别:
-
资助金额:$53.49万
-
财政年份:2019
-
负责人:Mingyao Li
-
依托单位:
Single-Cell Transcriptomic Analysis of Human Retina
-
批准号:10119528
-
项目类别:
-
资助金额:$41.35万
-
财政年份:2019
-
负责人:Mingyao Li
-
依托单位:
Single-Cell Transcriptomic Analysis of Human Retina
-
批准号:9920150
-
项目类别:
-
资助金额:$56.1万
-
财政年份:2019
-
负责人:Mingyao Li
-
依托单位:
Single-Cell Transcriptomic Analysis of Human Retina
-
批准号:10396650
-
项目类别:
-
资助金额:$52.94万
-
财政年份:2019
-
负责人:Mingyao Li
-
依托单位:
Statistical Methods for Single-Cell Transcriptomics
-
批准号:9402782
-
项目类别:
-
资助金额:$38.16万
-
财政年份:2017
-
负责人:Mingyao Li
-
依托单位:
Statistical Methods for Single-Cell Transcriptomics
-
批准号:10005375
-
项目类别:
-
资助金额:$37.29万
-
财政年份:2017
-
负责人:Mingyao Li
-
依托单位:
Statistical Methods for Transcriptome Profiling Using RNA Sequencing
-
批准号:8840978
-
项目类别:
-
资助金额:$29.59万
-
财政年份:2014
-
负责人:Mingyao Li
-
依托单位:
Statistical Methods for Transcriptome Profiling Using RNA Sequencing
-
批准号:9026310
-
项目类别:
-
资助金额:$2.7万
-
财政年份:2014
-
负责人:Mingyao Li
-
依托单位:
Statistical Methods for Transcriptome Profiling Using RNA Sequencing
-
批准号:8998966
-
项目类别:
-
资助金额:$29.57万
-
财政年份:2014
-
负责人:Mingyao Li
-
依托单位:
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease
-
批准号:9751923
-
项目类别:
-
资助金额:$79.73万
-
财政年份:2012
-
负责人:Mingyao Li
-
依托单位:
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic Disease
-
批准号:8827410
-
项目类别:
-
资助金额:$51.73万
-
财政年份:2012
-
负责人:Mingyao Li
-
依托单位:
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease
-
批准号:10460231
-
项目类别:
-
资助金额:$70.59万
-
财政年份:2012
-
负责人:Mingyao Li
-
依托单位:
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic Disease
-
批准号:8273057
-
项目类别:
-
资助金额:$74.77万
-
财政年份:2012
-
负责人:Mingyao Li
-
依托单位:
海外基金