arXiv:2605.11022q-bio.GNcs.AI2026-05

用对比学习嵌入序列,高效识别原核生物操纵子对。

SCOPE: Siamese Contrastive Operon Pair Embeddings for Functional Sequence Representation and Classification

论文配图:SCOPE: Siamese Contrastive Operon Pair Embeddings for Functional Sequence Representation and Classification
图 1 · 摘自论文原文
  • 设计双胞胎MLP模型融合蛋白语言模型嵌入,提升分类性能。
  • 在DGEB数据集上达到0.71的ROC-AUC,媲美顶尖模型。
  • 适合需要大规模基因组注释与调控网络重建的研究者。

识别操纵子是理解原核生物基因调控的基础,将基因分类为操纵子有助于重建调控网络、注释未标注基因及药物候选开发。实验方法如RT-PCR和RNA-seq虽准确,但耗时且仅限于模式生物,因此亟需可扩展的计算方法。现有计算方法多采用逻辑回归等传统分类器,我们以此作为物理化学特征基线。DGEB基准通过预训练蛋白语言模型独立嵌入序列并计算成对余弦相似度评估操纵子对分类。相比之下,我们的双胞胎MLP在融合嵌入空间上学习分类器,理论上更适合二分类任务,因余弦相似度受嵌入模型正则化影响可能产生无意义得分。尽管蛋白语言模型嵌入在ROC-AUC上显著优于物理化学特征,但学习的双胞胎MLP头在平均精度上未显著超越无监督余弦相似度,表明嵌入空间几何已充分捕捉功能关系。然而,我们的模型仍取得0.71的ROC-AUC,与当前最优模型相当。结果表明,蛋白语言模型嵌入是跨多样微生物基因组进行操纵子对分类的可行、可扩展基础,对自动化基因组注释、调控网络重建及缺乏实验注释生物体的表征具有重要意义。

原文摘要 · Abstract (English)

Identifying operons is a fundamental step in understanding prokaryotic gene regulation, as classifying genes into operons supports the reconstruction of regulatory networks, functional annotation of unannotated genes, and drug candidate development. Experimental approaches such as RT-PCR and RNA-seq provide precise evidence of operon structure, but are laborious and largely limited to well-studied model organisms, making scalable computational methods essential for genome-wide operon identification. Prior computational approaches have employed traditional classifiers such as logistic regression and decision trees, motivating our use of these as physicochemical baselines. The DGEB benchmark evaluates operonic pair classification by embedding each sequence independently with a pre-trained protein language model and computing pairwise cosine similarity. In contrast, our Siamese MLP learns a classifier over the fused embedding space, which is theoretically better motivated for binary classification, as cosine similarity can yield meaningless scores depending on the regularization of the embedding model. While protein language model embeddings substantially outperform physicochemical features in ROC-AUC, a learned Siamese MLP head does not significantly improve over unsupervised cosine similarity in Average Precision, suggesting that the geometry of the embedding space already captures the functional relationships needed for this task. Nonetheless, our Siamese MLP achieves a ROC-AUC of 0.71, competitive with state-of-the-art models on the DGEB leaderboard. These findings indicate that protein language model embeddings are a viable, scalable foundation for operonic pair classification across diverse microbial genomes, with implications for automated genome annotation, regulatory network reconstruction, and characterization of organisms lacking experimental operon annotations.

基因组分析序列嵌入机器学习操纵子识别

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