Methods for improving clinical diagnostic by detection, prediction, interpretation and prioritization of aberrant transcriptome variations
Methods for improving clinical diagnostic by detection, prediction, interpretation and prioritization of aberrant transcriptome variations
批准号:
10674723
负责人:
Yoseph Barash
金额:
$33.99万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-08-03 至 2025-07-31
关键词:
AddressAdoptedAgeAlgorithmsAlternative SplicingBenchmarkingCellsChildClinVarClinicalCodeComplexComputersDNAData AnalysesData SetDefectDetectionDevelopmentDiagnosisDiagnosticDiseaseEventExcisionExclusionExhibitsExonsGenderGenesGeneticGenetic DiseasesGenetic TranscriptionGenetic VariationGenomicsGenotype-Tissue Expression ProjectGoalsHumanInternationalLettersLibrariesManualsMedicalMendelian disorderMessenger RNAMethodsModelingMolecular DiagnosisMutationNormal tissue morphologyOutcomePathogenicityPatientsPediatric HospitalsPerformancePhenotypePhiladelphiaPositioning AttributeProgram Research Project GrantsProtein IsoformsProteinsRNARNA ProcessingRNA SplicingRegulationReverse Transcriptase Polymerase Chain ReactionSamplingSiteTechnologyTestingTissuesTrainingUnited States National Institutes of HealthUntranslated RNAVariantVisualizationWorkcandidate identificationcausal variantclinical applicationclinical diagnosisclinical diagnosticscohortcomputational pipelinescongenital anomalydeep learning modelexomeexome sequencingfollow-upgenetic testinggenetic variantheterogenous dataimprovedinterestmRNA Precursornovelprediction algorithmpredictive modelingprogramsrare mendelian disorderstandard of caretooltranscriptometranscriptome sequencing
中文摘要
本研究计划的目标是发展方法,以改善儿童的临床诊断
英文摘要
The goal of this research program project is to develop methods to improve clinical diagnosis of children with
rare Mendelian disorders. Even with the most advanced standard-of-care genetic test of exome sequencing (ES)
diagnostic rate is still below 50%. One reason for this rate is that mutations in non-protein coding regions or
those that are synonymous (code for the same protein) are generally discarded even though these could be
deleterious due to their effect on the processing of RNA transcribed from the underlying gene. We propose 2
complementary methods to help improve clinical diagnosis: The first is “RNA-first”, where our algorithms suggest
which clinically accessible tissue (CAT) to use for RNA sequencing, then compare the results to a larger pool of
donors to detect which RNA processing variations may be deleterious. The second is a “DNA-first” approach
where we develop “RNA splicing code” models that predict the effect of genetic variations on RNA processing in
a given tissue of interest. The two approaches, “RNA-first” and “DNA-first”, will be combined into a clinical
diagnostic pipeline at the Children Hospital of Philadelphia (CHOP) and applied to solve undiagnosed cases at
CHOP and other centers, including the NIH’s Undiagnosed Disease Network (UDN).
期刊论文(6)
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DOI:
10.1186/s13059-021-02411-1
发表时间:
2021-06-28
期刊:
Genome biology
影响因子:
12.3
作者:
[Schulz L, Torres-Diz M, Cortés-López M, Hayer KE, Asnani M, Tasian SK, Barash Y, Sotillo E, Zarnack K, König J, Thomas-Tikhonenko A]
通讯作者:
Thomas-Tikhonenko A
DOI:
10.1093/nar/gkad1043
发表时间:
2024-01-05
期刊:
NUCLEIC ACIDS RESEARCH
影响因子:
14.9
作者:
[Quesnel-Vallieres, Mathieu, Jewell, San, Lynch, Kristen W., Thomas-Tikhonenko, Andrei, Barash, Yoseph]
通讯作者:
Barash, Yoseph
DOI:
10.1186/s13059-022-02681-3
发表时间:
2022-05-17
期刊:
Genome biology
影响因子:
12.3
作者:
[]
通讯作者:
Contrasting and Combining Transcriptome Complexity Captured by Short and Long RNA Sequencing Reads.
对比和组合短和长 RNA 测序读取捕获的转录组复杂性。
DOI:
10.1101/2023.11.21.568046
发表时间:
2023
期刊:
bioRxiv : the preprint server for biology
影响因子:
--
作者:
[Han,SeongWoo, Jewell,San, Thomas-Tikhonenko,Andrei, Barash,Yoseph]
通讯作者:
Barash,Yoseph
Identifying regulatory uORFs as a targetable axis for hereditary disease
-
批准号:10709564
-
项目类别:
-
资助金额:$40.4万
-
财政年份:2022
-
负责人:Yoseph Barash
-
依托单位:
Identifying regulatory uORFs as a targetable axis for hereditary disease
-
批准号:10504131
-
项目类别:
-
资助金额:$39.45万
-
财政年份:2022
-
负责人:Yoseph Barash
-
依托单位:
Identifying regulatory uORFs as a targetable axis for hereditary disease
-
批准号:10797954
-
项目类别:
-
资助金额:$7.64万
-
财政年份:2022
-
负责人:Yoseph Barash
-
依托单位:
Methods for improving clinical diagnostic by detection, prediction, interpretation and prioritization of aberrant transcriptome variations
-
批准号:10451556
-
项目类别:
-
资助金额:$33.99万
-
财政年份:2020
-
负责人:Yoseph Barash
-
依托单位:
Methods for improving clinical diagnostic by detection, prediction, interpretation and prioritization of aberrant transcriptome variations
-
批准号:10033447
-
项目类别:
-
资助金额:$34.77万
-
财政年份:2020
-
负责人:Yoseph Barash
-
依托单位:
Methods for improving clinical diagnostic by detection, prediction, interpretation and prioritization of aberrant transcriptome variations
-
批准号:10227951
-
项目类别:
-
资助金额:$34.66万
-
财政年份:2020
-
负责人:Yoseph Barash
-
依托单位:
Methods for RNA splicing variations detection, quantification, visualization, and association from large heterogeneous datasets
-
批准号:9895303
-
项目类别:
-
资助金额:$7.17万
-
财政年份:2018
-
负责人:Yoseph Barash
-
依托单位:
Cassette exons in neoplastic pro-B-cells: implications for immunotherapy
-
批准号:10578300
-
项目类别:
-
资助金额:$42.04万
-
财政年份:2018
-
负责人:Yoseph Barash
-
依托单位:
Methods for RNA splicing variations detection, quantification, visualization, and association from large heterogeneous datasets
-
批准号:9500401
-
项目类别:
-
资助金额:$43.25万
-
财政年份:2018
-
负责人:Yoseph Barash
-
依托单位:
Cassette exons in neoplastic pro-B-cells: implications for immunotherapy
-
批准号:10228864
-
项目类别:
-
资助金额:$18.53万
-
财政年份:2018
-
负责人:Yoseph Barash
-
依托单位:
Modeling Splicing in normal tissues and neurodegenerative disease
-
批准号:9285730
-
项目类别:
-
资助金额:$32.32万
-
财政年份:2014
-
负责人:Yoseph Barash
-
依托单位:
Modeling Splicing in normal tissues and neurodegenerative disease
-
批准号:8759380
-
项目类别:
-
资助金额:$31.52万
-
财政年份:2014
-
负责人:Yoseph Barash
-
依托单位:
Modeling Splicing in normal tissues and neurodegenerative disease
-
批准号:8912349
-
项目类别:
-
资助金额:$30.97万
-
财政年份:2014
-
负责人:Yoseph Barash
-
依托单位:
海外基金