合成致命连接和图形变压器改善了合成致命性预测
Kunjie Fan1, Birkan Gökbağ1, Shan Tang2
1Department of Biomedical Informatics, College of Medicine, The Ohio State University, 1800 Cannon Drive, Columbus, OH 43210, United States.
Briefings in bioinformatics
|August 29, 2024
概括
合成死亡率 (SL) 预测模型对于癌症点发现至关重要. 一个新的多层编码器 (MLEC-iSL) 有效地预测SL相互作用,改善了CRISPR双击实验的基因对选择.
科学领域:
- 计算生物学和生物信息学
- 基因组学和癌症研究
背景情况:
- 合成致死性 (SL) 是一种有前途的策略,用于识别新的癌症点.
- 目前的CRISPR双击 (CDKO) 技术在全基因组查能力方面是有限的.
- 缺少可扩展和通用化的SL属性,阻碍了预测建模工作.
研究的目的:
- 开发一个强大的,可扩展和可通用的SL预测模型.
- 改进用于CDKO实验的基因对的选择.
- 为了确定癌症治疗的新型SL相互作用.
主要方法:
- 开发了一种新的两步多层编码器,用于单个样本特定的SL预测 (MLEC-iSL).
- MLEC-iSL集成了基因,图形和变压器编码器,以预测SL连接和相互作用.
- 使用K562和Jurkat细胞系和22Rv1细胞中的CDKO实验验验证了MLEC-iSL性能.
主要成果:
- 在K562 (AUPR 0.73,AUC 0.72) 和Jurkat (AUPR 0.73,AUC 0.71) 细胞中,MLEC-iSL实现了高预测性能,优于现有方法.
- 在22Rv1细胞的实验验证显示,在987个选择的基因对中,SL率为46.8%.
- 这项研究揭示了细胞亡和细胞分裂细胞死亡途径之间的SL依赖性.
结论:
- SL连接是一种适合预测建模的可扩展和通用性质.
- 在预测SL相互作用和指导CDKO实验方面,MLEC-iSL表现出卓越的性能.
- 这些发现突出了通过合成致死性在癌症中潜在的治疗点和途径.
相关概念视频
02:26Protein Networks
3.9K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
3.9K
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K