通过使用基因组规模的代谢模型和突变数据来预测与癌症体质突变相关的代谢物
GaRyoung Lee1,2, Sang Mi Lee1,2, Sungyoung Lee3
1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Genome biology
|March 12, 2024
概括
这项研究引入了一种计算工作流程,通过将突变与代谢途径联系起来来识别致癌的代谢物. 这种方法有助于发现癌症治疗的新治疗点.
科学领域:
- 计算生物学是一种计算生物学.
- 癌症代谢 癌症代谢
- 基因组学就是基因组学.
背景情况:
- 由基因突变产生的代谢物,在积累时促进癌症.
- 鉴定突变相关代谢物对于癌症治疗至关重要,但由于细胞复杂性而具有挑战性.
- 多个基因有助于癌症的发展,使代谢物识别复杂化.
研究的目的:
- 开发一个计算工作流来预测代谢物-基因路径集.
- 为了确定与癌症体位突变显著相关的代谢物和代谢途径.
- 为了促进新型代谢物的发现,并为癌症治疗策略提供信息.
主要方法:
- 开发了一个计算工作流程,将癌症患者特定的基因组规模代谢模型 (GEM) 与突变数据集成在一起.
- 运用omics数据 (突变,RNA序列,代谢组) 进行细胞特异GEM构建和工作流程验证.
- 根据急性髓性白血病和细胞癌的多组数据以及18种癌症类型的公开可用的RNA-seq数据进行验证的预测.
主要成果:
- 计算工作流成功预测了与体质突变相关的代谢物-基因路径集.
- 验证证实了许多代谢物/代谢途径和特定的体质突变之间的显著关联.
- 工作流程通过确定关键代谢物-基因路径链接来证明治疗潜力.
结论:
- 开发的计算工作流有效地预测了癌症中的代谢物-基因-通路关联.
- 这种方法有助于识别新的代谢物和潜在的癌症治疗点.
- 这些发现支持使用计算方法来推进癌症代谢研究和治疗.
相关概念视频
02:21Cancers Originate from Somatic Mutations in a Single Cell
11.9K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.9K
02:53Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
02:43Mouse Models of Cancer Study
5.5K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.5K
01:20Mismatch Repair
4.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K