题  目：AI驱动的未知蛋白系统挖掘

报告人：常乘　军事科学院军事医学研究院

Abstract：已有研究表明，尚有大量非经典开放阅读框（non-canonical open reading frames, ncORFs）翻译而来的未知蛋白质有待深入挖掘，而这些未知蛋白质往往在重要的生理、病理过程中发挥关键调控作用。系统挖掘这些未知蛋白质，即“蛋白质组中的暗物质（Dark Proteome）”，将有助于深入理解生命系统复杂性。为此，我们开发了基于自监督学习的蛋白质组预训练模型π-SPECFormer，以2.91亿张质谱谱图为训练数据，通过对比学习框架理解谱图中的潜在规律，并应用于从头测序、谱图聚类、翻译后修饰鉴定等下游任务，均取得显著的性能提升。进一步，将π-SPECFormer应用于一组人类蛋白质组数据的重分析时，谱图、肽段和蛋白层面的鉴定量分别提升了280.0%、128.7%和25.8%，发现了大量包含修饰和突变的新蛋白。这表明蛋白质组预训练模型具有巨大的应用价值和潜力，为系统挖掘未知蛋白提供了新思路。

题  目：The evolutionary process of pathogenic variation in DNA damage repair genes

报告人：李嘉恒　成都大熊猫繁育研究基地

Abstract：DNA damage repair (DDR) genes play critical roles in maintaining genome stability. However, they are prone to genetic variation, of which the pathogenic variation (PVs) is the predisposition causing high risk of cancer in modern humans. Knowing the origin of DDR PVs is critical for understanding the genetic basis of cancer risk in modern humans. So far, there is no consent for the original sources of DDR PVs in modern humans. We performed phylogenic analysis and the results ruled out non-human species as the original source for the PVs in modern humans through evolution conservation. We performed anthropological analyses by tracing the PVs from modern humans in over 5,000 ancient humans spanning the past 40,000 years. Our comprehensive investigation reveals that DDR PVs was mainly originated from recent evolutionary history of modern humans, and highlights that the high cancer risk caused by DDR PVs in modern humans is the by-products of human evolutionary process.

题  目：The Conservation of Giant Panda under Ex- and In-situ perspective

报告人：王也　成都大熊猫繁育研究基地

Abstract：Since the 1980s, advances in captive breeding and disease control have produced a self‑sustaining ex‑situ population that retains 97.68% genetic diversity—surpassing long‑term management targets. Ex‑situ efforts have generated key technologies for field conservation, including non‑invasive sampling, genetic resource banking, disease surveillance, and AI‑based identification. These tools support health monitoring in panda habitats, vaccination programs to reduce pathogen spillover, and standardized rescue‑and‑release protocols, with eight wild pandas successfully returned to nature. The program also enhances capacity building and public education. Together, these outcomes illustrate how well‑designed ex‑situ conservation can directly reinforce in‑situ protection while providing a vital safeguard for endangered species.

题  目：驯化基因组中的“寄生虫”

报告人：杨斧　星空游戏(StarSky Sports)官方网站

Abstract：Retrotransposons are highly enriched in the animal genome. The activation of retrotransposons can rewrite host DNA information and fundamentally impact host biology. Although developmental activation of retrotransposons can offer benefits for the host, such as against virus infection, uncontrolled activation promotes disease or potentially drives ageing. After activation, retrotransposons use their mRNA as templates to synthesize double-stranded DNA for making new insertions in the host genome. Although the reverse transcriptase that they encode can synthesiz the first-strand DNA, how the second-strand DNA is generated remains largely unclear. Here we report that retrotransposons hijack the alternative end-joining (alt-EJ) DNA repair process of the host for a circularization step to synthesize their second-strand DNA. We used Nanopore sequencing to examine the fates of replicated retrotransposon DNA, and found that 10% of them achieve new insertions, whereas 90% exist as extrachromosomal circular DNA (eccDNA). Using eccDNA production as a readout, further genetic screens identified factors from alt-EJ as essential for retrotransposon replication. alt-EJ drives the second-strand synthesis of the long terminal repeat retrotransposon DNA through a circularization process and is therefore necessary for eccDNA production and new insertions. Together, our study reveals that alt-EJ is essential in driving the propagation of parasitic genomic retroelements. Our study uncovers a conserved function of this understudied DNA repair process, and provides a new perspective to understand—and potentially control—the retrotransposon life cycle.

题  目：高通量高灵敏度单细胞蛋白质组学方法开发

报告人：杨云　广东智慧医学国际研究院

Abstract：单细胞蛋白质组学能带来对生命活动更全面更深层的理解，人体蛋白质组导航国际大科学计划（π-HuB）将构建单细胞分辨率的人体蛋白质组图谱，但是面临低检测通量和低灵敏度的两大技术瓶颈。本次报告将介绍基于质谱的单细胞蛋白质组学技术的发展历程及本团队在高通量高灵敏度单细胞蛋白质组学方法开发方面的最新进展。我们针对卵母细胞等通常手工挑选的细胞，开发了一种简单的、基于样品瓶的一步式样品前处理方法SOViP（JACS Au (2025) 5: 2321），将样品制备时间缩短至1小时内，手动操作时间仅需几分钟。使用SOViP技术，我们能从单个小鼠和人的卵母细胞中分别定量检测约7000和8000种蛋白质。另外，为了大幅提高质谱检测的通量，我们开发了一种结合多种标记试剂的联用方法，并实现了标记过程的自动化操作（bioRxiv 2025）。针对不同标记试剂报告离子响应差异导致的定量偏差，我们开发了两种归一化方法，大幅提高了定量准确性。我们的方法达到了每天检测2000个单细胞的超高通量，并且能从HeLa等单细胞中定量检测约2000个蛋白，兼顾了高通量和高灵敏度。结合使用保留时间对齐工具DeepRTAlign（Nature Communications (2023) 14:8188）和质谱组队等技术，我们将有望实现单细胞蛋白质组学的大规模应用。