Informatics Platform for Mammalian Gene Regulation at Isoform-level
异构体水平的哺乳动物基因调控信息学平台
基本信息
- 批准号:10273985
- 负责人:
- 金额:$ 34.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-11-01 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAlgorithmic AnalysisAlgorithmsAllelesAlternative SplicingArchitectureBioinformaticsBiological AssayBipolar DisorderBrain NeoplasmsCRISPR/Cas technologyCancer PatientCell LineCellsClassificationCluster AnalysisComputer softwareComputing MethodologiesDNA-Binding ProteinsDataData SetDerivation procedureDevelopmentDiagnosisDiseaseEpigenetic ProcessExonsGene ExpressionGene Expression RegulationGenesGeneticGenetic TranscriptionGenomeGenomicsGlioblastomaGoalsHumanHuman GenomeInformaticsKnowledgeLabelLuciferasesMalignant NeoplasmsMammalian CellMethodsMolecularMusMutationNeurodegenerative DisordersNormal tissue morphologyParkinson DiseasePatternPhenotypeProtein IsoformsQuantitative Trait LociRNA SplicingRegulationRegulator GenesReporterResearchSamplingSchizophreniaSignal PathwaySiteSpecimenStatistical Data InterpretationStatistical MethodsStratificationTissue SampleTranscriptUpdateVariantautism spectrum disorderbasebioinformatics toolcancer subtypeschromatin immunoprecipitationclassification algorithmdata integrationdata miningdiagnostic biomarkerdiscrete datafeature selectiongene functiongene productgenetic signaturegenome editinggenome-wide analysishigh dimensionalityimprovedin silicoinnovationmolecular diagnosticsmultiple omicsneuropsychiatric disordernovelopen sourceoutcome forecastplatform-independentprediction algorithmprogramspromoterprotein functionpublic health relevancetherapeutic targettooltranscriptometranscriptome sequencingtumoruser friendly softwareuser-friendly
项目摘要
SUMMARY
With each successive discovery in genetics, the true dynamic complexity of the human genome has become
increasingly apparent, requiring relatively consistent updates to the technical definition of the word “gene”. It is
now understood that the notion of “one gene makes one protein that functions in one signaling pathway” in
human cells is overly simplistic, because majority of the human genes produce multiple functional products
(transcript variants and protein isoforms), through alternative transcription and/or alternative splicing.
Therefore, our central hypothesis is that the isoform-level gene products – “transcript variants” and “protein
isoforms” are the basic functional units in a mammalian cell, and accordingly, the informatics platforms for
managing and analyzing gene regulation data both in normal and disease cells should adopt “gene isoform
centric” rather than “gene centric” approaches. Towards the goal of broadly impacting gene regulation and
functional studies at gene isoform-level, we have been developing novel algorithms for analyses of genome-
wide transcriptome (RNA-seq and exon-array) and protein-DNA binding (ChIP-seq) data, and for extending the
gene-level orthology mapping to exon- and transcript-level mapping between the orthologous human and
mouse genes. By applying these novel algorithms on public datasets, we have observed significant expression
differences between different sample groups (e.g., developmental stages, cancer subtypes, normal vs cancer)
for numerous genes at the isoform-level but not at the overall gene-level, and experimentally validated the
`significant' isoforms using RT-qPCR in independent bio-specimens. While the application of these algorithms
has led to the development of new methods for diagnosis of glioblastoma or a sub-type thereof, the isoform-
level transcriptome analyses results also led to some challenging questions – for example – How are the
alternative promoters of a gene show switch-like opposing patterns of activity (while one promoter is up- the
other is down-regulated in one condition vs the other), and how are different splice-variants of a gene show
opposing expression patterns in cancer versus normal tissue samples? We currently lack informatics methods
to address these challenging questions. Therefore, we propose to develop novel statistical methods (1) for
integrative cluster analysis of isoform-level gene expression information from exon-array and RNA-seq
platforms, (2) for identification of differential transcript/isoform usage in heterogeneous cancer samples, and
(3) for identification of alternative transcription/splicing quantitative trait locus (sQTL) in tumor adjusted by
somatic genetic and epigenetic changes. And, (4) the novel predictions from these algorithms will be
experimentally validated by performing Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay
and CRISPR/Cas9 genome editing in U87 and A172 cells. The novel bioinformatics methods developed by this
project will help in silico discovery and research for accelerating the linkage of phenotypic and genomic
information, at gene-isoform level.
总结
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RAMANA V DAVULURI其他文献
RAMANA V DAVULURI的其他文献
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{{ truncateString('RAMANA V DAVULURI', 18)}}的其他基金
Developing novel deep-learning based methods for deciphering non-coding gene regulatory code
开发基于深度学习的新型方法来破译非编码基因调控密码
- 批准号:
10451673 - 财政年份:2021
- 资助金额:
$ 34.36万 - 项目类别:
Developing novel deep-learning based methods for deciphering non-coding gene regulatory code
开发基于深度学习的新型方法来破译非编码基因调控密码
- 批准号:
10615784 - 财政年份:2021
- 资助金额:
$ 34.36万 - 项目类别:
Informatics Platform for Mammalian Gene Regulation at Isoform-level
异构体水平的哺乳动物基因调控信息学平台
- 批准号:
9922347 - 财政年份:2013
- 资助金额:
$ 34.36万 - 项目类别:
Informatics Platform for Mammalian Gene Regulation at Isoform-level
异构体水平的哺乳动物基因调控信息学平台
- 批准号:
8843951 - 财政年份:2013
- 资助金额:
$ 34.36万 - 项目类别:
Informatics platform for mammalian gene regulation at isoform-level
异构体水平的哺乳动物基因调控信息学平台
- 批准号:
8658144 - 财政年份:2013
- 资助金额:
$ 34.36万 - 项目类别:
Genomewide discovery & analysis of alternative promoters
全基因组发现
- 批准号:
7678211 - 财政年份:2006
- 资助金额:
$ 34.36万 - 项目类别:
Genomewide discovery & analysis of alternative promoters
全基因组发现
- 批准号:
7226994 - 财政年份:2006
- 资助金额:
$ 34.36万 - 项目类别:
Genomewide discovery & analysis of alternative promoters
全基因组发现
- 批准号:
7371108 - 财政年份:2006
- 资助金额:
$ 34.36万 - 项目类别:
Genomewide discovery & analysis of alternative promoters
全基因组发现
- 批准号:
7033451 - 财政年份:2006
- 资助金额:
$ 34.36万 - 项目类别:
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