相关实验视频

Updated: Jul 12, 2025

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Published on: August 21, 2016

DNA语言模型是全基因组变异效应的强有力的预测器

Gonzalo Benegas¹, Sanjit Singh Batra², Yun S Song^2,3,4

¹Graduate Group in Computational Biology, University of California, Berkeley, CA 94720.

Proceedings of the National Academy of Sciences of the United States of America

|October 26, 2023

概括

基因组预训练网络 (GPN) 使用DNA序列的无监督学习来预测全基因组的遗传变异效应. 这种计算方法的性能优于现有的工具,有助于在像Arabidopsis thaliana这样的物种中识别变异.

科学领域:

基因组学就是基因组学.
生物信息学是一种生物信息学.
计算生物学计算生物学

背景情况:

全基因组关联研究 (GWAS) 识别与特征相关的遗传变异,但确定因果变异是具有挑战性的.
遗传变异的实验验证是昂贵和耗时的,需要可扩展的计算预测方法.
在蛋白质序列分析中取得成功的无监督学习,为预测基因组DNA的变异效应提供了一个有希望的途径.

研究的目的:

引入基因组预训练网络 (GPN),这是一种用于预测全基因组遗传变异效应的新型无监督模型.
为了证明GPN能够在没有监督的情况下学习基因结构和DNA动机的能力.
通过使用Arabidopsis thaliana数据评估GPN在预测功能变异影响方面的表现.

主要方法:

开发了基因组预训练网络 (GPN) 模型,用于基因组DNA序列的无监督预训练.
在Arabidopsis thaliana和七种相关的Brassicales物种的非对齐参考基因组上训练了GPN.
使用来自1001基因组项目和GWAS数据的等位基因频率评估了GPN的预测准确性.

主要成果:

在没有监督的情况下,GPN成功地学习了全基因组变异效应,基因结构和DNA动机.
与保存分数 (phyloP,phastCons) 相比,GPN在预测遗传变异的功能影响方面表现优越.
对Arabidopsis thaliana的预测变异效应在UCSC基因组浏览器中可视化.

结论:

GPN提供了一种准确且可扩展的计算方法,用于预测全基因组变异效应.
无监督方法使任何物种只使用其DNA序列来预测变异效应.
GPN促进了GWAS发现的解释,并加速了因果变异的识别.

关键词:

阿拉比多普西斯塔利亚纳 (Arabidopsis thaliana) 是一种植物.全基因组关联研究研究.语言模型语言模型机器学习是机器学习.变体效应预测变体效应预测

更多相关视频

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Published on: January 9, 2020

相关概念视频

DNA as a Genetic Template

DNA as a Genetic Template

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...

Genome-wide Association Studies-GWAS

Genome-wide Association Studies-GWAS

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...

Comparing Copy Number Variations and SNPs

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

Evolutionary Relationships through Genome Comparisons

Evolutionary Relationships through Genome Comparisons

Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...

Next-generation Sequencing

Next-generation Sequencing

The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....

Incomplete Dominance

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.