一种模块化蛋白质语言建模方法,用于免疫性预测
Hugh O'Brien1, Max Salm1, Laura T Morton1
1Achilles Therapeutics UK Ltd, United Kingdom.
PLoS computational biology
|November 11, 2024
概括
预测新抗原免疫性对于个性化医学至关重要. 蛋白质语言模型ImmugenX改进了CD8+T细胞表皮质免疫性预测,优于现有方法,并提供了对模型偏差的见解.
科学领域:
- 计算生物学是一种计算生物学.
- 免疫信息学是指免疫信息学.
- 个性化医疗是个性化的医疗.
背景情况:
- 预测新抗原免疫性对于开发个性化癌症疫苗至关重要.
- 在这个预测任务中,有限的培训数据和低的反应率构成了重大挑战.
研究的目的:
- 介绍ImmugenX,一种新的模块化蛋白质语言建模方法,用于预测CD8+T细胞表皮图免疫性.
- 评估ImmugenX的性能与预测pMHC相互作用和免疫性方面的最先进模型相比.
主要方法:
- 开发了ImmugenX,一个模块化框架,包含pMHC和可选的TCR编码模块.
- 训练了pMHC编码模块进行预测任务,包括结合亲缘关系,解解联体预测和稳定性.
- 使用了特定于背景的免疫原性预测头模块.
主要成果:
- ImmugenX的编码模块在pMHC结合亲和力,解联体预测和稳定性任务上表现相似或优越.
- 在pMHC免疫性预测 (AUC=0.619,AP=0.514) 方面,ImmugenX显著优于现有模型,平均精度提高了7%.
- 整合T细胞受体 (TCR) 语境进一步增强了免疫性预测性能.
结论:
- ImmugenX提供了一种强大而改进的方法,用于预测CD8+表位的新抗原免疫性.
- 该模型的解释性分析发现了当前模型的弱点和公共数据集中的潜在偏差.
- ImmugenX促进了有效的个性化免疫疗法的发展.
相关概念视频
02:50Conjugated Proteins
18.2K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.2K
02:28Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
02:40Ligand Binding Sites
12.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.7K
01:26Antigens Involved in Adaptive Immunity
460
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
460