The Cancer Atlas Microbiome provides a clearer picture of microbiota living in organs

Biomedical engineers at Duke University have designed an algorithm to remove contaminated microbial genetic information from The Cancer Genome Atlas (TCGA). With a clearer picture of the microbiota living in several organs both in healthy and cancerous states, researchers will now be able to detect new biomarkers of disease and gain a better understanding of how several cancers are affects the human body.

In the first study using the newly contaminated data, the researchers have already found that normal and cancerous organ tissues have a slightly different microbiota concentration, that bacteria from these diseased sites enter the bloodstream, and this bacterial information may help in cancer detection and prediction. patient outcomes.

The results will appear online on December 30 in the magazine Cell Host & Microbe.

TCGA is a unique cancer genomics program that appeared molecularly in more than 20,000 primary cancers and matched healthy samples spanning 33 cancer types. It has generated more than 2.5 million gigabytes of “omic” data. The atlas includes what DNA is present, what epigenetic markers are on the DNA, what DNA is turned on and what proteins are made. It is freely available for public use.

One study from the atlas data revealed an abundance of Fusobacterium nucleatum in colorectal cancer, which has since been shown to be indicative of the stage, survival, metastasis and even drug responses of this type of cancer. Many more studies have found such bacterial biomarkers, but few have been found. Pollution is a major cause of this. When bacteria are inadvertently introduced into the samples by the laboratories, it will be difficult to determine which species were in the samples at first. While microbial studies such as the use of microbial-rich materials such as feces can overcome small contaminants, the relatively small samples taken from living human organs and tumor samples cannot.

When examining a subset of TCGA sequencing data, previous studies found that microbial DNA from several species was the result of laboratory contamination.

“Every microbiota study is corrupted by the idea that, if you find a microphone, was it really in the old material or was contamination introduced during processing?” Xiling Shen said. , Hawkins Family Associate Professor of Biomedical Engineering at Duke. “We have created a method that extracts the microbes that were actually in each sample and used it to build what we call the Cancer Microbiome Atlas, which will be a great resource for the community. and allows us to understand how cancer changes. organ midge. “

The method for removing contamination from TCGA data was devised by Anders Dohlman, a graduate student in Shen’s laboratory. Dohlman first compared the microbiome names between cancerous tissues from different organs and blood, and removed contaminants that appeared undifferentiated. He then compared microbiome signatures of identical samples processed at individual sites, from Harvard to Baylor. Dohlman concluded that the microbial species found only from a specific site are the contaminants, allowing him to assign a specific contaminant signature to each site.

“A major challenge in this process was species with mixed evidence, which are bacteria that are both polluting and endogenous to the material,” Dohlman said. “But because TCGA has so many different types of data, we were able to pull it out. Big data helps!”

The effort is already paying dividends in a number of ways. After using Dohlman’s decontamination algorithm, the researchers looked closely at microbiota signatures of samples taken from colorectal cancer patients. They found two distinct groups of bacteria that are often found together, one of which appears to be related to patient survival.

The researchers also found that some cancers actually alter the microorganisms of their resident organs. It may be, for Shen reasons, that tumors alter an organ’s microenvironment, making it larger or more hostile to different microphone species. And by looking for microbial signatures within a patient’s blood samples, they also found that, despite conventional wisdom to the contrary, some bacteria find their way into the bloodstream. , which may be a sign of cancer progression.

“There has been a kind of urgency in the field as to whether or not high-profile papers can be reproduced, due to a pollution challenge,” Shen said. “For example, while one facility would be able to reproduce its results, another center would not. This explains why: Each facility has its own consistent bias. (Its own residential microbe pollutants. ) In the future, new studies may use our method to remove this bias and reproduce results, and research centers may be able to use the bias we have identified to mitigate their pollution. “