Y-Trim：基于证据的适配酶尾修剪用于单链亚硫酸盐测序
Y-Trim: Evidence-gated Adaptase tail trimming for single-stranded bisulfite sequencing
AI总结：
Y-Trim通过基于证据的决策框架，解决单链亚硫酸盐测序中无模板适配酶尾部修剪的不确定性问题，提供可解释的预处理策略。
摘要：
背景：单链全基因组亚硫酸盐测序（ssWGBS）能够在低输入和高度碎片化的材料中进行DNA甲基化分析，包括游离DNA。在广泛使用的亚硫酸盐后处理协议中，适配酶介导的尾部添加会引入随机、无模板的末端序列。与适配器定义的接头不同，这些尾部没有固定的序列模板，因此修剪必须在FASTQ阶段通过内在不确定性决定。\n\n结果：我们证明亚硫酸盐诱导的组成退化意味着在有限的核苷酸字母表下，任何固定的每读取边界规则都会有一个严格正的误差底座。受这一限制的指导，我们引入了Y-Trim，一个基于证据的框架，将准入（我们是否修剪）与推断（在哪里修剪）分开。对于Read 2，Y-Trim通过一个固定的、化学类型化的矩阵线性纹理评分方案实现每读取自适应的切割位置；对于Read 1，它在读取级别定位受限时使用自动化样本级别锚定。在各个模块中，Y-Trim是一个明确的、针对化学反应的决策规则，具有可解释的操作点。在经过整理的34次运行公共队列（CCGB-34）和具有已知潜在边界模拟器压力测试中，Y-Trim在Read 2操作行为上表现出稳定性，并在Read 1可行性受限行为上与条件读取通过一致。\n\n结论：无模板的适配酶尾修剪最好被视作一个受证据限制的FASTQ阶段决策，而不是一个通用的预处理调节器。通过使可接受性和回避显式化，并暴露可解释的基因组保留与残余携带量的权衡，Y-Trim为ssWGBS提供了一个实用的不确定性感知预处理策略。
英文摘要：
Background: Single-stranded whole-genome bisulfite sequencing (ssWGBS) enables DNA methylation profiling in low-input and highly fragmented material, including cell-free DNA. In widely used post-bisulfite protocols, Adaptase-mediated tailing adds stochastic, template-free end sequence. Unlike adapter-defined junctions, these tails lack a fixed sequence template, so trimming must be decided from FASTQ-stage observables under intrinsic uncertainty. Results: We show that bisulfite-induced compositional degeneracy implies a strictly positive error floor for any fixed per-read boundary rule under a finite nucleotide alphabet. Guided by this limit, we introduce Y-Trim, an evidence-gated framework that separates admission (should we trim) from inference (where to trim). For Read 2, Y-Trim performs per-read adaptive cut placement via a fixed, chemistry-typed matrix-linear texture scoring scheme; for Read 1, it uses automated sample-level anchoring when read-level localization is feasibility-limited. Across modules, Y-Trim is an explicit, chemistry-specific decision rule with interpretable operating points. On a curated 34-run public cohort (CCGB-34) and simulator stress tests with known latent boundaries, Y-Trim exhibits stable Read 2 operating behavior and Read 1 feasibility-limited behavior consistent with conditional read-through. Conclusions: Template-free Adaptase tail trimming is best viewed as an evidence-limited FASTQ-stage decision rather than a generic preprocessing knob. By making admissibility and abstention explicit and exposing interpretable genomic-retention versus residual-carryover trade-offs, Y-Trim provides a practical uncertainty-aware preprocessing strategy for ssWGBS.
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