Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA, USA.
Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Methods Mol Biol. 2025;2867:153-168. doi: 10.1007/978-1-0716-4196-5_9.
The JCVI-Syn3 organism is a minimal organism derived from Mycoplasma mycoides capri, which is capable of self-replication. While the ancestor has 863 genes, the synthetic progeny has only 473, with 434 of these coding for proteins. Despite initial efforts to understand all functions of the organism, a significant number of these protein-coding genes still have unknown functions, and subsequent studies have been only partially successful in elucidating their roles. In this study, we employ our innovative method PROST to identify homologs and better understand these previously unidentified genes. PROST employs protein language embeddings and enables the identification of remote homologs with as low as 16% sequence identity. PROST successfully finds functionally annotated homologs for 93% of the minimal genome with a high level of accuracy, both confirming previously identified functions, as well as proposing new functions for others. The results of our study can be accessed at https://bit.ly/prost-syn3a .
JCVI-Syn3 生物体是源自山羊支原体的最小自我复制生物体。虽然其祖先有 863 个基因，但合成的后代只有 473 个，其中 434 个编码蛋白质。尽管最初努力了解生物体的所有功能，但这些蛋白质编码基因中有相当数量的功能仍然未知，随后的研究仅部分成功地阐明了它们的作用。在这项研究中，我们采用了我们的创新方法 PROST 来识别同源物并更好地理解这些以前未识别的基因。PROST 使用蛋白质语言嵌入，并能够以低至 16%的序列同一性识别远程同源物。PROST 成功地为最小基因组的 93%找到了具有高精度的功能注释同源物，既确认了先前确定的功能，也为其他功能提出了新的功能。我们的研究结果可在 https://bit.ly/prost-syn3a 上获得。
