Department of Research, Advanta Genetics, Tyler, TX, United States.
Soules College of Business, University of Texas at Tyler, Tyler, TX, United States.
Front Cell Infect Microbiol. 2023 Jul 4;13:1221289. doi: 10.3389/fcimb.2023.1221289. eCollection 2023.
Urinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data.
Precision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity.
Results revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0-3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment.
PM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.
尿路感染（UTI）仍然是一个诊断挑战，常常导致抗生素过度使用。尽管尿液培养是 UTI 诊断的金标准，但一些尿路病原体可能导致假阴性或不确定的结果。虽然 PCR 检测快速且高度敏感，但它的诊断效果仅限于靶向微生物。宏基因组下一代测序（mNGS）是一种无需假设即可破译尿生物群的方法。然而，临床上相关的信息往往隐藏在大量的测序数据中。
精准宏基因组学（PM）是一种基于杂交捕获的方法，具有增强发现能力和更好的诊断效果的潜力，同时不会稀释临床上相关的信息。我们收集了 47 份临床疑似 UTI 的尿液样本，同时对每个样本进行微生物培养、PCR 和 PM 检测；然后，我们比较分析了结果。接下来，我们使用 Explify®数据分析平台对累积微生物群进行表型分类，以确定潜在的致病性。
结果显示，PM 与培养结果具有 100%的阳性预测一致性（PPA），仅鉴定出 13 种不同的微生物，而 PCR 和 PM 分别鉴定出 19 种和 62 种微生物。所有鉴定出的微生物都被分类为表型组（0-3），随着致病性和临床相关性的增加。这种 PM 可以通过像 Explify®这样的生物信息学平台同时定量和表型分类微生物，实质上为及时和准确的经验性 UTI 治疗提供了分解和定量的结果。
PM 为在复杂的 UTI 疾病中建立超越常规护理检测的有效诊断模型提供了潜力。未来的研究应评估 PM 指导的 UTI 管理对临床结果的影响。
