title: Distinguishing potential bacteria-tumor associations from contamination in a secondary data analysis of public cancer genome sequence data.
abstract: A variety of bacteria are known to influence carcinogenesis. Therefore, we sought to investigate if publicly available whole genome and whole transcriptome sequencing data generated by large public cancer genome efforts, like The Cancer Genome Atlas (TCGA), could be used to identify bacteria associated with cancer. The Burrows-Wheeler aligner (BWA) was used to align a subset of Illumina paired-end sequencing data from TCGA to the human reference genome and all complete bacterial genomes in the RefSeq database in an effort to identify bacterial read pairs from the microbiome.
  
  
  
  Through careful consideration of all of the bacterial taxa present in the cancer types investigated, their relative abundance, and batch effects, we were able to identify some read pairs from certain taxa as likely resulting from contamination. In particular, the presence of Mycobacterium tuberculosis complex in the ovarian serous cystadenocarcinoma (OV) and glioblastoma multiforme (GBM) samples was correlated with the sequencing center of the samples. Additionally, there was a correlation between the presence of Ralstonia spp. and two specific plates of acute myeloid leukemia (AML) samples. At the end, associations remained between Pseudomonas-like and Acinetobacter-like read pairs in AML, and Pseudomonas-like read pairs in stomach adenocarcinoma (STAD) that could not be explained through batch effects or systematic contamination as seen in other samples.
  
  
  
  This approach suggests that it is possible to identify bacteria that may be present in human tumor samples from public genome sequencing data that can be examined further experimentally. More weight should be given to this approach in the future when bacterial associations with diseases are suspected.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Robinson
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crabtree
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: John S A
authors.initials: JS
authors.lastname: Mattick
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Anderson
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. jdhotopp@som.umaryland.edu.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. jdhotopp@som.umaryland.edu.|Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. jdhotopp@som.umaryland.edu.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Dunning Hotopp
mesh_terms: D000150:Acinetobacter / Q000235:genetics; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D002277:Carcinoma / Q000145:classification / Q000235:genetics* / Q000382:microbiology*; D000077216:Carcinoma, Ovarian Epithelial; D002874:Chromosome Mapping; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000382:microbiology; D030541:Databases, Genetic; D016680:Genome, Bacterial; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics / Q000382:microbiology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000382:microbiology*; D064307:Microbiota; D009169:Mycobacterium tuberculosis / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000382:microbiology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000382:microbiology; D011549:Pseudomonas / Q000235:genetics
keywords: Acinetobacter; Acute myeloid leukemia; Batch effects; Cancer; Cancer-associated bacteria; Genome sequencing; Microbiome; Pseudomonas; Stomach adenocarcinoma