Journalartikel

Autorenliste: Sepich-Poore, Gregory D.; Mcdonald, Daniel; Kopylova, Evguenia; Guccione, Caitlin; Zhu, Qiyun; Austin, George; Carpenter, Carolina; Fraraccio, Serena; Wandro, Stephen; Kosciolek, Tomasz; Janssen, Stefan; Metcalf, Jessica L.; Song, Se Jin; Kanbar, Jad; Miller-Montgomery, Sandrine; Heaton, Robert; Mckay, Rana; Patel, Sandip Pravin; Swafford, Austin D.; Korem, Tal; Knight, Rob

Jahr der Veröffentlichung: 2024

Zeitschrift: Oncogene

ISSN: 0950-9232

eISSN: 1476-5594

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1038/s41388-024-02974-w

Verlag: Springer Nature [academic journals on nature.com]

Abstract: 
In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2-12]. Given this impact, we carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested batch correction by comparing raw and Voom-SNM-corrected data per-batch, finding predictive equivalence and significantly similar features. We found consistent results with a modern microbiome-specific method (ConQuR [14]), and when restricting to taxa found in an independent, highly-decontaminated cohort. (2) Using Conterminator [15], we found low levels of human contamination in our original databases (similar to 1% of genomes). We demonstrated that the increased detection of human reads in Gihawi et al. [13] was due to using a newer human genome reference. (3) We developed Exhaustive, a method twice as sensitive as Conterminator, to clean RefSeq. We comprehensively host-deplete TCGA with many human (pan)genome references. We repeated all analyses with this and the Gihawi et al. [13] pipeline, and found cancer type-specific microbiomes. These extensive re-analyses and updated methods validate our original conclusion that cancer type-specific microbial signatures exist in TCGA, and show they are robust to methodology.

Harvard-Zitierstil: Sepich-Poore, G., Mcdonald, D., Kopylova, E., Guccione, C., Zhu, Q., Austin, G., et al. (2024) Robustness of cancer microbiome signals over a broad range of methodological variation, Oncogene. https://doi.org/10.1038/s41388-024-02974-w

APA-Zitierstil: Sepich-Poore, G., Mcdonald, D., Kopylova, E., Guccione, C., Zhu, Q., Austin, G., Carpenter, C., Fraraccio, S., Wandro, S., Kosciolek, T., Janssen, S., Metcalf, J., Song, S., Kanbar, J., Miller-Montgomery, S., Heaton, R., Mckay, R., Patel, S., Swafford, A., ...Knight, R. (2024). Robustness of cancer microbiome signals over a broad range of methodological variation. Oncogene. https://doi.org/10.1038/s41388-024-02974-w