18-Oct-2021 - Friedrich-Schiller-Universität Jena

Artificial intelligence helps to find new natural substances

New method enables fast and confident identification of previously unknown small molecules

More than a third of all medicines available today are based on active substances from nature and a research team from the University of Jena has developed a procedure to identify small active substance molecules much more quickly and easily. Secondary natural substances that occur in numerous plants, bacteria and fungi can be anti-inflammatory, can ward off pathogens or even prevent the growth of cancer cells. However, making use of the riches provided by nature’s medicine cabinet and identifying new natural substances is time-consuming, costly and labour-intensive. A team of bioinformaticians at Friedrich Schiller University Jena has now developed a method that enables much faster and easier identification of small active substance molecules. The researchers present their method, called COSMIC (Confidence Of Small Molecule IdentifiCations), in the current issue of the journal Nature Biotechnology.

Millions of structural data items not yet deciphered

To find out which substances are contained in a biological sample such as a plant extract, a researcher analyses the sample using mass spectrometry. In this process, the molecules are broken down into fragments and their mass is determined. “The CSI:FingerID molecule search engine we developed allows us to search specifically for molecular structures that match these fragments,” says Prof. Sebastian Böcker of the University of Jena. “Whether this search is successful – i.e., whether the search result represents the correct structure – is not something we can distinguish in this way.”

There are currently huge collections of data with billions of mass spectrometry data items from millions of analyses of biological samples, the vast majority of which have not been identified as to their structure. This is where COSMIC is now coming into play, enabling structures to be deciphered automatically for a large proportion of these as yet unidentified molecules. “To this end, we use machine-learning methods,” explains Martin Hoffmann, lead author of the new publication. “First, the mass spectrum of the sample under examination is compared with the available structural data.” As a result, you get – as in a Google search – a more or less extensive list of possible hits. “Our method now indicates how confident one can be that the hit found in the first place is actually the structure we are looking for,” Hoffmann adds. To do this, COSMIC determines a score that evaluates the quality of the suggested hit and deduces whether it is correct or incorrect.

New bile acids discovered

Böcker and his team have been able to demonstrate how well their method really works, in cooperation with colleagues from the University of California, San Diego. They studied mass spectrometry data from the digestive system of mice, searching for as yet unknown bile acids. For this purpose, more than 28,000 theoretically possible bile acid structures were constructed and compared with the measurement data from the microbiome of the mice. The subsequent analysis with COSMIC yielded a total of 11 new, previously completely unknown bile acid structures. Two of these have since been confirmed using specifically synthesised reference samples.

“This shows, firstly, that our method works reliably,” emphasises Sebastian Böcker. Secondly, COSMIC makes it possible to accelerate substantially the search for new and interesting substances, because the screening can be performed completely automatically, without any manual effort and in a very short time. Böcker expects that in the coming years, it will be possible to clarify thousands of new molecular structures in this way.

Facts, background information, dossiers

  • bile acids

More about Uni Jena

  • News

    How the first biomolecules could have been formed

    The chemical precursors of present-day biomolecules could have formed not only in the deep sea at hydrothermal vents, but also in warm ponds on the Earth's surface. The chemical reactions that may have occurred in this “primordial soup” have now been reproduced in experiments by an internat ... more

    Fitness needs the right timing

    Life on Earth runs in 24-hour cycles. From tiny bacteria to human beings, organisms adapt to alterations of day and night. External factors, such as changes in light and temperature, are needed to entrain the clock. Many metabolic processes are controlled by the endogenous clock. Scientists ... more

    Catalytic hydrogen generation – without expensive precious metals

    A research team from Friedrich Schiller University Jena has developed a molecular photosystem inspired by nature that generates hydrogen under visible light irradiation. In contrast to other existing systems of this type, it functions without the use of precious or heavy metals. Low-cost an ... more

  • q&more articles

    Effective drug navigation in sepsis

    Many drug candidates never reach clinical use due to their side effects. For example, inhibitors of phosphoinositide 3-kinase-γ, a signaling protein that plays an important role in infections, cannot be used because of their side effects on the immune response. more

    Genes on sugar

    The targeted transport of DNA and RNA using vectors (mostly made from synthetic polymers) in cell cultures has become part of routine practice in biological R&D – a fact highlighted by the multitude of commercial kits now available. To date, however, obstacles relating to use in patients ha ... more

    Highly-prized components

    The isolation of bioactive plant ingredients, essential oils or dyes and flavourings of plant origin requires costly and sophisticated procedures. Several applications do not actually require isolation of the individual components, however – their concentration is sufficient. Moreover, for ... more

  • Authors

    Prof. Dr. Ulrich S. Schubert

    Ulrich S. Schubert, born in 1969, is Chair (W3) for Organic and Macromolecular Chemistry at Friedrich Schiller University Jena, Germany. He studied chemistry at the Universities of Frankfurt and Bayreuth and subsequently received his PhD from the Universities of Bayreuth and South Florida, ... more

    Prof. Dr. Thomas Heinze

    Thomas Heinze, born in 1958, studied chemistry at FSU Jena. After receiving his doctorate there in 1989 and subsequent postdoc work at KU Leuven (Belgium), he completed his habilitation in 1997. In 2001, he accepted a professorship in Macromolecular Chemistry at the University of Wuppertal ... more

    Prof. Dr. Dagmar Fischer

    Dagmar Fischer is a licensed pharmacist before obtaining her doctorate in pharmaceutical technology and biopharmacy from the Philipps University of Marburg in 1997. After a period spent at Texas Tech University Health Sciences Center (USA), she gained several years' experience as Head of Pr ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: