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

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

RAMANA V DAVULURI其他文献

RAMANA V DAVULURI的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:
Bioinformatics Facility
生物信息学设施
  • 批准号:
    7945001
  • 财政年份:
    2009
  • 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:

相似海外基金

How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
  • 批准号:
    2315783
  • 财政年份:
    2023
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
  • 批准号:
    2719534
  • 财政年份:
    2022
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633211
  • 财政年份:
    2020
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
  • 批准号:
    20K01113
  • 财政年份:
    2020
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2436895
  • 财政年份:
    2020
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633207
  • 财政年份:
    2020
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
  • 批准号:
    426559561
  • 财政年份:
    2019
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
  • 批准号:
    2236701
  • 财政年份:
    2019
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
  • 批准号:
    19K01745
  • 财政年份:
    2019
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
  • 批准号:
    415543446
  • 财政年份:
    2019
  • 资助金额:
    $ 34.36万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了