Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV 89557, USA; Integrative Neuroscience Program, University of Nevada, Reno, NV 89557, USA; Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV 89557, USA.
Gen Comp Endocrinol. 2024 Oct 1;357:114597. doi: 10.1016/j.ygcen.2024.114597. Epub 2024 Jul 29.
Neuropeptides are essential neuronal signaling molecules that orchestrate animal behavior and physiology via actions within the nervous system and on peripheral tissues. Due to the small size of biologically active mature peptides, their identification on a proteome-wide scale poses a significant challenge using existing bioinformatics tools like BLAST. To address this, we have developed NeuroPeptide-HMMer (NP-HMMer), a hidden Markov model (HMM)-based tool to facilitate neuropeptide discovery, especially in underexplored invertebrates. NP-HMMer utilizes manually curated HMMs for 46 neuropeptide families, enabling rapid and accurate identification of neuropeptides. Validation of NP-HMMer on Drosophila melanogaster, Daphnia pulex, Tribolium castaneum and Tenebrio molitor demonstrated its effectiveness in identifying known neuropeptides across diverse arthropods. Additionally, we showcase the utility of NP-HMMer by discovering novel neuropeptides in Priapulida and Rotifera, identifying 22 and 19 new peptides, respectively. This tool represents a significant advancement in neuropeptide research, offering a robust method for annotating neuropeptides across diverse proteomes and providing insights into the evolutionary conservation of neuropeptide signaling pathways.
神经肽是重要的神经元信号分子，通过在神经系统内和外周组织中的作用来协调动物的行为和生理。由于生物活性成熟肽的体积较小，使用现有的生物信息学工具（如 BLAST）在蛋白质组范围内对其进行鉴定具有很大的挑战性。为了解决这个问题，我们开发了 NeuroPeptide-HMMer（NP-HMMer），这是一种基于隐马尔可夫模型（HMM）的工具，用于促进神经肽的发现，特别是在研究较少的无脊椎动物中。NP-HMMer 使用经过人工策展的 HMM 来识别 46 种神经肽家族，能够快速准确地识别神经肽。NP-HMMer 在果蝇、水蚤、谷象和黄粉虫上的验证表明，它能够有效地识别不同节肢动物中的已知神经肽。此外，我们通过在 Priapulida 和轮虫中发现新的神经肽来展示 NP-HMMer 的实用性，分别鉴定出 22 种和 19 种新肽。该工具代表了神经肽研究的重大进展，提供了一种强大的方法来注释不同蛋白质组中的神经肽，并深入了解神经肽信号通路的进化保守性。
