视觉转换器为多基因风险启发的框架揭示了前列腺癌中潜在的遗传异质性
James V Talwar1,2, Adam Klie1,2, Meghana S Pagadala3
1Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA.
medRxiv : the preprint server for health sciences
|June 4, 2025
概括
一种新的深度学习模型VADEr通过分析遗传数据相互作用,准确预测复杂疾病风险. 它确定了关键的遗传驱动因素和亚型,为个性化医学提供了可解释的见解.
科学领域:
- 基因组学就是基因组学.
- 人工智能的人工智能
- 计算生物学 计算生物学
背景情况:
- 多基因风险评分 (PRS) 传统上评估遗传责任,但通常假定特征独立.
- 遗传变异之间的复杂相互作用对于准确预测疾病风险至关重要.
- 深度学习架构,特别是变压器,擅长捕捉特征依赖.
研究的目的:
- 介绍VADEr,一个视觉转换器启发的架构,用于基因型到表型的预测.
- 为了改善疾病风险评估,在遗传数据中建模本地和全球相互作用.
- 开发DARTH评分,以可解释地识别遗传风险驱动因素.
主要方法:
- 开发了VADEr,这是一个集成NLP和计算机视觉技术的深度学习模型,用于基因数据分析.
- 应用VADEr以使用遗传变异数据预测前列腺癌 (PCa) 风险.
- 制定了基于注意力的DARTH分数,以将风险贡献归因于特定的基因组区域.
主要成果:
- 在多个指标 (精度,平均精度,MCC) 上预测PCa风险方面,VADEr显著超过了基准方法.
- DARTH评分确定了关键的PCa风险位点 (例如HOXB13,TMPRSS2,MSMB),并揭示了遗传异质性.
- DARTH得分突出了特定位置 (例如,LMTK2) 和PCa分子亚型 (例如,SPOP) 之间的关联.
结论:
- VADEr有效地捕获遗传变异依赖性,推进复杂疾病的基因型到表型预测.
- DARTH分数提供了对个性化遗传风险因素的可解释的见解.
- 瓦德-达斯框架为PCa等复杂疾病的精准医学提供了一个有希望的方向.
相关概念视频
01:11Genome-wide Association Studies-GWAS
13.2K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.2K
01:33Cancer-Critical Genes I: Proto-oncogenes
8.7K
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...
8.7K
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
01:20The Retinoblastoma Gene
4.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
01:33Pleiotropy
40.3K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.3K
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