While researchers have typically seen microbes only as contaminants and discarded them, Micronoma has set itself apart by seeing the treasure trove of opportunity microbes represent to detect and identify cancer early.

Using liquid biopsy–a simple blood draw–Micronoma is looking at signals coming from microbes that may be associated with cancer in a biologically relevant manner, while finding ways to separate them from others that would likely be technical contamination. 

Indeed, make no mistake, every sample used by researchers has some potential level of microbial contamination. The key is clearing the contamination away to isolate the biologically relevant microbes that will indicate cancer, as Micronoma has discovered how to do. 

As scientists know, contamination can come from any number of sources, including the environment or even bacteria, viruses, or fungi on the skin that comes in contact with the needle that draws the blood sample. 

Micronoma’s work, ultimately published in Nature, “clearly indicates that the biomarkers we see in our samples are biologically relevant and not just technical contaminants,” Micronoma Co-founder and Chief Executive Officer Sandrine Miller-Montgomery said.

Micronoma’s team, with its decades of expertise working with microbes, is well aware that microbial contamination is a possibility at multiple steps of the process, from sample collection to final report. To address the issue, Micronoma has developed a rigorous system of proprietary controls at multiple steps of its research process to ensure it filters out contaminants. The team then sorts through what is left of the relevant microbes to find cancer signals.

Some of the positive and negative controls are incorporated at the wet lab level during sample processing, and others are incorporated during data analysis at the dry lab level. 

As a simplified overview, when Micronoma takes in the samples, it starts by accounting for a watchlist of the “usual suspects” of contamination and the amount of each found in samples that are nothing more than distractions in the data. 

After checking samples against the watchlist, the team starts to put in place its controls to start distinguishing between microbes that could indicate the presence of cancer and those that are simply contaminants and not pertinent to cancer detection..

As it looks at all microbiome signals in the samples, Micronoma uses tools that enable it to easily remove any glaring contaminants present–such as from the environment or sample collection process–to further refine the picture. In addition, to the extent there are any environmental contaminants not accounted for through that process, they would be present in all samples, meaning they would have little weight in our results.

There is not one magic filter used to decontaminate samples. There are multiple levels of decontamination done in highly specific manners.

Though Micronoma has always seen it as a best practice and high priority to use those proper controls throughout its workflow, the point cannot be emphasized enough that the Micronoma team is not basing its findings on contamination, but real biological signals indicating the presence of cancer.

The combination of all these controls ensures that what Micronoma sees is a true biological signal so that each sample produces accurate results.

It is also worth noting that our Oncobiota™ platform’s classification performance cannot be attributed to outside contaminants not eliminated by workflow controls. Doing so would mean that outside contaminants somehow were not only present in samples collected at various times, from different places, and among healthy or unhealthy patients, but also present in a differential manner that can distinguish between lung cancer and other lung disease, cancers or even healthy adjacent tissues.

It is very unlikely a surgeon could contaminate two samples collected from a given patient (cancer tissue and adjacent healthy tissue, for example), during the same surgical procedure, with two different microbial populations. It is even less likely that those two different microbial populations would then occur across multiple surgeries or even healthcare centers. A biological difference is a more rational explanation.

Though the process is proprietary, Miller-Montgomery likened it to the restoration of an old painting that reveals finer details in the art that were covered up at some point. While observers of the pre-restoration painting might have thought they saw the full picture the artist was trying to present, they did not.

Jan Vermeer’s, “Girl Reading a Letter at an Open Window”  Image 1, Before restoration, Image 2, After restoration. (From “How art restorers uncover hidden details in artworks” on DW.com)

Micronoma’s process does the same thing for cancer diagnosis: It reveals the fine detail of microbial signals no one else thought to look closely enough to find or what simply was not visible behind a “screen” of contamination.

 Importantly, while the contamination removal process has worked very well, it was done with enough precision that Micronoma has not had to discard any of its samples for not being able to render a result due to “over decontamination.”

 “What has really been interesting to us, and we take as a good sign about the quality of our samples, is that we are not getting samples that are too contaminated to use,” Miller-Montgomery said.

 “It’s a balance to make sure that you’re not, to go back to the painting analogy, over-washing the painting and then removing too much,” Miller-Montgomery said. “You want to remove the right layer. The process leaves enough of a relevant microbiological signal so that we can still draw the conclusion.” 

 In the end, Micronoma’s robust decontamination protocol provides confidence that its patent pending Oncobiota™ platform will produce an accurate, clean, and informative picture.

“We’re not naïve,” Miller-Montgomery said. “We know contaminants exist. And we know very well that you have to remove them if you want to have a robust analysis. That’s one of the reasons our methodology is working. The importance of decontamination was absolutely key.”