Durham, North Carolina – Duke University biomedical engineers have devised an algorithm to remove contaminated microbial genetic information from the Cancer Genome Atlas (TCGA). With a clearer picture of the microbes that live in different organs in both health and cancer conditions, researchers will now be able to find new biomarkers of disease and better understand how many cancers affect the human body.
In the first study using a newly cleared dataset, researchers have already discovered that normal and cancerous organ tissues have a slightly different microbiota composition, that bacteria from these diseased sites can enter the bloodstream, and that this bacterial information can help diagnose cancer and predict patient outcomes. .
The results appear online Dec.30 in the journal Cell and microbe host.
TCGA is a landmark cancer genomics program that molecularly features over 20,000 primary cancers and identical healthy samples covering 33 types of cancer. It generated more than 2.5 million gigabytes of “omic” data. The atlas includes the DNA found, the epigenetic markers on the DNA, the DNA that is played back, and the proteins that are produced. It is freely available for public use.
One study drawn from the Atlas data revealed an abundance of Fusobacterium nuclei in colorectal cancer, which has since been shown to indicate stage, survival, metastasis and even pharmacological responses to this type of cancer.
Several other studies have looked for such bacterial biomarkers, but few have been discovered. A big reason for this is pollution. When bacteria are accidentally introduced into samples by laboratories, it becomes difficult to determine which species were already present in the samples to begin with. While similar microbiome studies using materials rich in microbes such as faeces can cope with small amounts of contamination, relatively small samples taken from living human organs and tumor samples cannot.
Upon examining a subset of TCGA sequence data, previous analyzes found that microbial DNA from a number of species was a result of laboratory contamination.
“All microorganism studies suffer from the idea that if a microbe was found, was it really present in the tissues or was contamination introduced during treatment?” Said Shiling Chen, associate professor of the Hawkins family in biomedical engineering at Duke. “We invented a method that could extract the microbes that were already present in every sample and used it to build what we called the Cancer Microbiome Atlas, which will be a tremendous resource for the community and allow us to understand how a cancer is changing the organ microbiome.”
The method for decontaminating TCGA data was invented by Anders Dohlman, a graduate student in Shen Lab. Dühlmann first compared the microbiome signatures between cancer tissue from different organs and blood, and excluded contaminated species that appeared randomly. Then compare the microbiome signatures of identical samples that were processed at separate sites, ranging from Harvard to Baylor. Dolman concluded that the microbial species that could only be detected from a specific site would be the contaminants, allowing him to assign a unique pollution signature to each site.
“The big challenge in this process was mixed evidence species, which is a contaminated bacterium that is endogenous to tissues,” Dühlmann said. “But since TCGA has so many different types of data, we were able to derive it. Big data really helps!”
This effort is already paying off in a number of ways. After using Dohlman’s algorithm to decontaminate the contamination, researchers took a closer look at the germs signatures of samples taken from colorectal cancer patients. They frequently discovered two unique groups of bacteria that co-exist together, and one of them appears to be linked to patient survival.
Researchers have also discovered that some cancers actually alter the microbiome of their resident organs. The reason, depending on Shin’s causes, may be that tumors alter the microenvironment of an organ, making it more or less suitable for different microbial species. By looking for microbial signatures in a patient’s blood samples, they also found that despite conventional wisdom indicating the opposite, some bacteria find their way into the bloodstream, which may also provide an indication of cancer progression.
“There was some kind of crisis in the field over whether or not high-ranking papers could be reproduced, due to the pollution challenge,” said Shen. For example, while one center will be able to reproduce its results, another will not. This explains why: Every position has a very stable bias. (Their resident microbial pollutants.) In the future, new studies can use our method to remove this bias and reproduce the results, and research centers may be able to use their bias that we have identified to mitigate their contamination. ”
This research was supported by the National Institutes of Health (R35GM122465, DK119795) and Defense Advanced Research Projects Agency (W911NF1920111).
Quote: “The Cancer Microbiome Atlas: A Comparative Analysis of Cancer Pan to Distinguish between Tissue Microorganisms and Contaminants.” Anders B. Dolman, Diana Arguijo Mendoza, Changle Deng, Michael Gao, Holly Dressman, Elian D. Iliffe, Stephen M. Lipkin, Schilling Chen. Cell and microbe host2021. DOI: 10.1016 / j.chom.2020.12.001