使用RaptGen发现生成性适配体。

Generative aptamer discovery using RaptGen.

作者信息

Iwano Natsuki, Adachi Tatsuo, Aoki Kazuteru, Nakamura Yoshikazu, Hamada Michiaki

机构信息

Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.

RIBOMIC, Tokyo, Japan.

出版信息

Nat Comput Sci. 2022 Jun;2(6):378-386. doi: 10.1038/s43588-022-00249-6. Epub 2022 Jun 2.

Abstract

Nucleic acid aptamers are generated by an in vitro molecular evolution method known as systematic evolution of ligands by exponential enrichment (SELEX). Various candidates are limited by actual sequencing data from an experiment. Here we developed RaptGen, which is a variational autoencoder for in silico aptamer generation. RaptGen exploits a profile hidden Markov model decoder to represent motif sequences effectively. We showed that RaptGen embedded simulation sequence data into low-dimensional latent space on the basis of motif information. We also performed sequence embedding using two independent SELEX datasets. RaptGen successfully generated aptamers from the latent space even though they were not included in high-throughput sequencing. RaptGen could also generate a truncated aptamer with a short learning model. We demonstrated that RaptGen could be applied to activity-guided aptamer generation according to Bayesian optimization. We concluded that a generative method by RaptGen and latent representation are useful for aptamer discovery.

摘要

核酸适配体是通过一种称为指数富集配体系统进化(SELEX)的体外分子进化方法产生的。各种候选物受到来自实验的实际测序数据的限制。在这里,我们开发了RaptGen,这是一种用于计算机模拟适配体生成的变分自编码器。RaptGen利用轮廓隐马尔可夫模型解码器来有效地表示基序序列。我们表明,RaptGen基于基序信息将模拟序列数据嵌入到低维潜在空间中。我们还使用两个独立的SELEX数据集进行了序列嵌入。即使高通量测序中未包含这些适配体,RaptGen也能从潜在空间中成功生成适配体。RaptGen还可以通过短学习模型生成截短的适配体。我们证明,根据贝叶斯优化,RaptGen可应用于活性导向的适配体生成。我们得出结论,RaptGen的生成方法和潜在表示对于适配体发现很有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144a/10766510/b3c1b27667e5/43588_2022_249_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索