Malva scans global cell data for cancer-typical RNA patterns in seconds
“The RNA is the cell’s transportable blueprint for a protein,” explained developer and systems biologist Prof. Dr. Nikolaus Rajewsky. Malva, a search engine built by a team at Berlin’s Max Delbrück Center (MDC), scans cell data from studies worldwide for RNA patterns linked to cancer in seconds, dekade-gegen-krebs.de reported. The work was published in the journal Nature a few months ago.
Rajewsky, a theoretical physicist and scientific director of the Berlin Institute for Medical Systems Biology at the MDC, leads research that combines single-cell biology, genomics and artificial intelligence to detect and understand diseases at the cellular level.
Why researchers needed a search engine for RNA
Personalized medicine now generates enormous amounts of RNA data, especially through single-cell analysis. Where researchers once analyzed clumps of cells and got average values, they can now examine a single tumor cell to see which genes are active in it. That view reveals the mechanisms at work in different parts of a tumor, because tumors contain very different cells with different growth strategies — a diversity responsible for treatment resistance and relapse.
Until now, that data treasure lay scattered across individual databases. Researchers had to download the large datasets one by one and evaluate them manually, which also required IT skills.
Malva solves that problem. The team processed publicly accessible study data into a single search index, so researchers can search it without downloading anything. A program continuously monitors public data archives for new datasets, which expand Malva’s index after processing.
What researchers can ask Malva
“If I find an RNA sequence in a cancer tissue now, I can ask Malva whether it is specific to this tumor type,” Rajewsky explained. Malva then shows in which previously studied cells the sequence was already found, along with the cell type and whether the cells came from healthy or diseased tissue.
A missing hit does not prove the RNA does not exist elsewhere, and whether a sequence actually triggers a disease or enables therapy resistance still requires further investigation. But Malva can evaluate any form of RNA sequence, including ones never before seen in humans, Rajewsky emphasized.
One way such variants arise is alternative splicing, in which the cell processes RNA differently. Different variants can emerge from a single gene’s blueprint, leading to different proteins. Cancer cells deliberately use such variants to promote their growth, division or resilience through the altered proteins. Malva therefore tells researchers not only which gene is active in a cell, but also which RNA variant the cell produces from it — something other tools cannot distinguish.
From research tool to potential cancer therapy targets
Knowing the proteins that drive uncontrolled cell growth opens the door to blocking them with modern cancer therapies. RNA analyses help find those proteins and point to a potential attack point — a “target” — against the cancer. The target must be specific to the tumor, though. If it also occurs frequently in healthy tissues, attacking it would cause severe side effects. “You have to be very careful there if you don’t want to harm the patient,” Rajewsky warned. An RNA sequence found only in the tumor could be a promising therapeutic target, and if it appears in several tumor types, a personalized therapy tailored to it could work across tumors.
The team is not working on concrete treatment strategies itself. The project is designed as a research tool, not a finished diagnostic or therapy platform. Rajewsky sees his task as using RNA to better understand “what kind of disease it is and how it will develop or how it will respond to certain treatments.” Concrete therapies would then have to be developed together with other specialists.
The team plans a spin-off to pursue work on potential therapeutic targets together with companies. For the academic research community, Malva will remain free to use, Rajewsky emphasized.
Questions researchers still ask about Malva
Is Malva a diagnostic tool for cancer patients? No. The project is explicitly a research tool, not a finished diagnostic or therapy platform, according to Rajewsky. It helps scientists understand diseases and their likely course, while concrete therapies must be developed with other specialists.
Can Malva find RNA sequences no one has seen before? Yes. Rajewsky emphasized that Malva can evaluate any form of RNA sequence, including variants never previously observed in humans, such as those produced through alternative splicing.
Does Malva cost money to use? For the academic research community, Malva stays free. A planned spin-off will handle work with companies on potential therapeutic targets.
Rajewsky’s goal is to use RNA to understand what a disease is, how it will develop, and how it will respond to specific treatments.
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