A biomedical engineer at Duke University has devised an algorithm that removes the genetic information of contaminated microorganisms from the Cancer Genome Atlas (TCGA). With clearer images of the microflora inhabiting different organs in both healthy and cancerous states, researchers find new biomarkers of the disease and how many cancers affect the human body. You will be able to understand better.
In the first study using a newly decontaminated dataset, researchers found that the composition of the microflora of normal and cancerous organ tissues was slightly different, and that bacteria from these affected areas were in the bloodstream. Outcomes of patients who have already discovered that they may enter and that this bacterial information may be useful in diagnosing and predicting cancer.
Results will be displayed online in the journal on December 30th Cell hosts and microorganisms..
TCGA is a breakthrough cancer genomics program that molecularly characterizes over 20,000 primary cancers and matches healthy samples across 33 cancer types. Generated over 2.5 million gigabytes of “omic” data. The atlas includes which DNA is present, which epigenetic markers are on the DNA, which DNA is on, and which proteins are being produced. It is open to the public freely.
One study from Atlas data revealed the abundance of fusobacterium nucleatum in colorectal cancer and has since shown a stage, survival, metastasis, and even drug response for this type of cancer. I have. More studies have searched for such bacterial biomarkers, but few have been found. The main reason for this is pollution. If bacteria are accidentally brought into a sample in the laboratory, it will be difficult to identify which species was actually included in the sample in the first place. Similar microbial flora studies using microbial-rich materials such as feces can overcome small amounts of contamination, but relatively small samples taken from living human organs and tumor samples.
Examining a subset of TCGA sequence data, previous analyzes found that microbial DNA from many species was the result of laboratory contamination.
“All microbiota studies are plagued by the idea that if a microbe is found, it is really in the tissue or the contamination was introduced during the process.” Hawkins Biomedical Engineering, Duke University. Associate Professor Xiling Shen said. “We invented a method that could extract the microbes that are truly contained in each sample and used it to build what we call the” cancer microbiome atlas. ” Organ microbiome. “
The method of removing contamination from TCGA data was invented by Anders Dorman, a graduate student in Shen’s lab. Dohlman first compared the microbiome characteristics between cancerous tissue and blood in various organs and ruled out indiscriminately appearing contaminants. We then compared the same sample of microbiome signatures processed at different sites, from Harvard University to Baylor University. Dohlman was able to conclude that pollutants are microbial species that can only be detected from specific locations and assign each location a unique contamination signature.
“A major challenge in this process was mixed evidence of pollutants and tissue-endogenous bacteria,” says Dohlman. “But TCGA has so many types of data that we were able to pull it out. Big data really helps!”
The effort has already paid dividends in various ways. After using Dorman’s decontamination algorithm, the researchers examined the microbiota characteristics of samples taken from patients with colorectal cancer. They found two unique groups of bacteria that are often found together, one of which appears to be associated with patient survival.
Researchers have also found that some cancers actually alter the microbiome of their resident organs. Shen’s reason may be that the tumor alters the microenvironment of the organ and is more or less kind to different microbial species. By looking for microbial characteristics in the patient’s blood sample, we also found that, contrary to conventional wisdom, some bacteria could invade the bloodstream and indicate cancer progression.
“There was some kind of crisis in this area about whether we could duplicate the paper that attracted attention because of pollution problems,” Shen said. “For example, one center can reproduce the results, but another cannot. This explains why. Each center has its own very consistent bias (unique resident microbial contamination). Substances.) How to remove this bias in new studies and reproduce the results in the future. Research centers may be able to use the biases we have identified to reduce contamination. “
This study was supported by the National Institutes of Health (R35GM122465, DK119795) and the Defense Advanced Research Projects Agency (W911NF1920111).
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