研究评估唾液样本替代血液用于大规模全基因组测序的可行性
Pilot Evaluation of Saliva Samples as An Alternative to Blood for Large-scale Whole-genome Sequencing Studies
一项先导研究建立了端到端的自动化全基因组测序（WGS）流程，涵盖机器人 DNA 提取、文库制备、测序和质量控制，并在该流程中比较唾液与血液来源样本。唾液与血液的胚系变异检测结果在全基因组范围内一致性达 97%，在高置信度基因组区域超过 99%；DNA 质量和测序质量等关键指标相当，而唾液样本的单样本成本更低。研究还比较了三种市售唾液采集试剂盒，均与配对血液样本达到至少 95% 的全基因组一致性，差异主要来自成本。在小规模配对比较中，自动化唾液处理的测序和短变异检测指标与手工处理大致相当。作者指出，需要更大规模、更多样化的研究来验证该先导结果的稳健性和可推广性。
来源：Genomics, Proteomics & Bioinformatics · doi.org
Whole-genome sequencing (WGS) studies have traditionally relied on blood as the primary DNA source and manual workflows. As population-based genomics studies expand, minimally invasive and easily deployable biospecimen collection methods compatible with high-throughput automation are increasingly needed. In this pilot study, we established a real-world, end-to-end automated WGS workflow, encompassing robotic DNA extraction, library preparation, sequencing and quality control. We compared saliva- and blood-derived WGS across key analytical parameters, including performance at each step of the workflow, overall cost, and feasibility for future large-scale implementation. First, germline variant calls from saliva and blood samples showed high concordance, reaching 97% genome-wide and over 99% in high-confidence genomic regions. Second, key workflow metrics, including DNA quality and sequencing quality, were comparable between saliva and blood samples, while saliva samples had a lower per-sample cost. We compared three commercially available saliva collection kits and found that all achieved at least 95% genome-wide concordance with matched blood samples, with differences primarily driven by cost. Finally, automated saliva processing produced sequencing and short variant calling metrics broadly comparable to manual processing in a small paired comparison. Collectively, these results provide a practical and scalable solution for incorporating saliva into future large cohort sequencing studies. Larger and more diverse studies are needed to further validate the robustness and generalizability of this pilot study.