Integrating MassQL and Molecular Networking to Identify Bioactive Compounds in Idesia polycarpa Maxim Idesia polycarpa Maxim (Salicaceae) is a well-studied plant producing various hydroxycyclohexenone (HCH) ester derivatives, which constitute most of its secondary metabolites. However, these major metabolites have been reported as unrelated to the alpha-melanocyte stimulating hormone (α-MSH) induced microphthalmia-associated transcription factor (MITF) expression observed in B16F10 melanoma cells, suggesting they may not be responsible for the antimelanogenic effect previously seen with the crude extract. To resolve this discrepancy and identify the bioactive metabolites in the crude extracts, the chemical diversity of I. polycarpa was reanalyzed using Mass Spec Query Language (MassQL)-enhanced molecular networking analysis, which indicated the presence of molecular families of phenolic glycosides without HCH esters. Following the MassQL-guided strategy to uncover the compounds responsible for the bioactivity, a targeted isolation study yielded five previously undescribed compounds and three known compounds, consistent with the MassQL annotations. Notably, one of the isolated non-HCH ester compounds, compound 1, demonstrated significant inhibition of α-MSH-induced melanogenesis via tyrosinase inhibition and MITF downregulation. This finding provides a potential explanation for the previously observed antimelanogenic activity of the crude extract, addressing the inconsistency associated with the major metabolites.

Cool new paper alert! 𝗜𝗻𝘁𝗲𝗴𝗿𝗮𝘁𝗶𝗻𝗴 𝗠𝗮𝘀𝘀𝗤𝗟 𝗮𝗻𝗱 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗮𝗿 𝗡𝗲𝘁𝘄𝗼𝗿𝗸𝗶𝗻𝗴 𝘁𝗼 𝗜𝗱𝗲𝗻𝘁𝗶𝗳𝘆 𝗕𝗶𝗼𝗮𝗰𝘁𝗶𝘃𝗲 𝗖𝗼𝗺𝗽𝗼𝘂𝗻𝗱𝘀 𝗶𝗻 𝙄𝙙𝙚𝙨𝙞𝙖 𝙥𝙤𝙡𝙮𝙘𝙖𝙧𝙥𝙖 𝗠𝗮𝘅𝗶𝗺 is a great example of how combining MassQL with molecular networking can cut through the noise and reveal bioactive compounds. Read more here: pubs.acs.org/doi/10.1021/....

Cool paper alert! 𝗔𝗻 𝗲𝘃𝗮𝗹𝘂𝗮𝘁𝗶𝗼𝗻 𝗺𝗲𝘁𝗵𝗼𝗱𝗼𝗹𝗼𝗴𝘆 𝗳𝗼𝗿 𝗺𝗮𝗰𝗵𝗶𝗻𝗲 𝗹𝗲𝗮𝗿𝗻𝗶𝗻𝗴-𝗯𝗮𝘀𝗲𝗱 𝘁𝗮𝗻𝗱𝗲𝗺 𝗺𝗮𝘀𝘀 𝘀𝗽𝗲𝗰𝘁𝗿𝗮 𝘀𝗶𝗺𝗶𝗹𝗮𝗿𝗶𝘁𝘆 𝗽𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗼𝗻 introduces a reproducible method for evaluating ML models that predict spectral similarity.

Read more here: bmcbioinformatics.biomedcentral.com/articles/10....

Congrats to the authors!

YouTube video by Ometa Labs Discovering Natural Products in Ometa Flow

Love natural products?

We do too! In our new video tutorial, we show you how to go from MS/MS data to a novel bioactive natural product produced across the tree of life - all in under 5 minutes.

Watch here: www.youtube.com/watch?v=hg79....

Mass spectrometry-based metabolomics approaches to interrogate host–microbiome interactions in mammalian systems Covering: 2015 to 2025Chemical crosstalk is universal to all life, niche-specific, and essential to thrive. This crosstalk is mediated by a large diversity of molecules, including metal ions, small mo...

How do microbes shape host biology - and how can we measure it? This excellent new review offers a comprehensive look at how to tackle this question.

Read the full text here: pubs.rsc.org/en/content/a...

Congrats to all the authors!

Peak Integration — Ometa Labs

Check out our new blog post on peak integration!

www.ometalabs.net/resources/pe...

The cool papers just keep coming!

𝘌𝘹 𝘝𝘪𝘷𝘰 Interaction Between Human Gut Microbiota and Artemisinin: A Multi-Omics Perspective explores how the antimalarial drug artemisinin is metabolized by the human gut microbiota.

Read more here: pmc.ncbi.nlm.nih.gov/articles/PMC...

Congrats to the authors!

The microbiome diversifies long- to short-chain fatty acid-derived N-acyl lipids Mass spectrometry data mining tools enabled the creation of an MS/MS spectral library containing hundreds of N-acyl lipids, including conjugates with short-chain fatty acids. This resource enabled the...

Cool new paper alert! 𝘛𝘩𝘦 𝘮𝘪𝘤𝘳𝘰𝘣𝘪𝘰𝘮𝘦 𝘥𝘪𝘷𝘦𝘳𝘴𝘪𝘧𝘪𝘦𝘴 𝘭𝘰𝘯𝘨- 𝘵𝘰 𝘴𝘩𝘰𝘳𝘵-𝘤𝘩𝘢𝘪𝘯 𝘧𝘢𝘵𝘵𝘺 𝘢𝘤𝘪𝘥-𝘥𝘦𝘳𝘪𝘷𝘦𝘥 𝘕-𝘢𝘤𝘺𝘭 𝘭𝘪𝘱𝘪𝘥𝘴 uses MassQL to identify over 750 new 𝘕-acyl lipids.

Read the full text here: www.cell.com/cell/fulltex...

Congrats to all the authors!

Banner announcing registration for beta testing of Ometa Lab's new MASST server.

Ometa MASST is coming - and we want your feedback!

We’re opening beta registration for the new Ometa Labs MASST server, purpose-built to bring high-throughput mass spectrometry search to the forefront of your research.

Register here: ometa-labs.neetoform.com/febd96405b1f...

Banner image with text Ometa Labs: the cutting edge features of GNPS, designed for industry.

Did you use GNPS during your academic career?

Ometa Labs adapts the cutting-edge workflows of GNPS for industry. This means one-on-one support and troubleshooting, enhanced data privacy, and custom development to fit your analysis needs.

Contact us to learn more: www.ometalabs.net/contact

Banner announcing registration for beta testing of Ometa Lab's new MASST server.

Beta test our new MASST server!

MASST is a revolutionary algorithm that can search billions of mass spectra in seconds. By beta testing, you'll get two weeks of unlimited searches free! Register here: ometa-labs.neetoform.com/febd96405b1f...

New to MASST? Learn more here: youtu.be/jAOj4XBFQEM?...

Mass spec comic from xkcd: https://m.xkcd.com/3094/

Potential activity for next year's #ASMS?

m.xkcd.com/3094/

Comparison of GNPS/GNPS2 and Ometa Labs. Ometa Labs provides GNPS2 workflows to businesses.

What's the difference between Ometa Labs and GNPS/GNPS2?

TL;DR: GNPS2 is great, but is only available for non-commercial use. Ometa Flow provides GNPS2 workflows to businesses, with analysis solutions, security, and support tailored to industry needs.

YouTube video by Ometa Labs What is MASST? Uncovering the Unknown in Mass Spectrometry

What is MASST?

At Ometa Labs, we're tackling one of metabolomic's biggest challenges: the fact that over 80% of small molecules go unannotated using traditional library searches.

MASST changes the game.

Learn more here: youtu.be/jAOj4XBFQEM?...

Don't miss the exciting announcement at the end!

Accelerating Natural Products Research with Ometa Flow — Ometa Labs Natural products and their derivatives make up the majority of FDA-approved small molecule drugs, yet natural products discovery still plays a small role in pharmaceutical R&D. Learn how Ometa Flo...

Natural products have shaped modern medicine, but their discovery is still challeneging. Our newest application note highlights how Ometa Flow can accelerate natural products discovery by going from raw data to lead compounds in less than 15 minutes. Read more here: www.ometalabs.net/application-...

Domain-Specific MASST — Ometa Labs

Ever looked at a compound and wondered: where have I seen this before? Domain-specific MASST can answer that question in seconds, and show where your compound is detected across microbes, plants, tissues, and more.

Learn more here: www.ometalabs.net/resources/do...

So exited to see this paper out! MassQL is game changing for compound identification (plus it's really fun to use!). You can read more about MassQL here: www.ometalabs.net/resources/ma....

Congrats to the authors!

I am thrilled to share after years of work/procrastination that the MassQL manuscript is finally published in @natmethods.nature.com - "A universal language for finding mass spectrometry data patterns". This was an team effort from all co-authors that helped shape MassQL and how it could be used.

Multispectrum ModiFinder Site Localization Performance - PubMed Tandem mass spectrometry (MS/MS) is a powerful technique for structural identification of small molecules, yet a significant portion of MS/MS spectra from untargeted experiments remain unidentifiable ...

In small‑molecule mass spec, we often treat spectral differences caused by adducts or collision energies as nuisances. But this new study flips that script and demonstrates a powerful way to predict chemical modifications.

Read more here: pubmed.ncbi.nlm.nih.gov/40202176/

Congrats to the authors!

YouTube video by Ometa Labs What is Ometa Flow?

Want to learn about Ometa Flow but only have 49 seconds?

Here you go!

youtu.be/U2aAHK8ysvU?...

#discovery #smallmolecules #metabolomics

Banner announcing new licensing tier that provides Ometa Flow for as low as $15K

Great news! We're rolling out a new licensing tier designed for smaller teams.

These licenses include all the tools and workflows Ometa has to offer, along with our best-in-class expert support. Learn more on our website: www.ometalabs.net.

Open-source System Suitability: Mass Spectrometry Query Language Lab (MassQLab) Reproducible analytical instrumentation system performance is critical for mass spectrometry, particularly metabolomics, aptly named system suitability testing. We identified a need based on literatur...

Really cool paper applying MassQL to system suitability testing: www.authorea.com/doi/full/10..... Congrats to the authors Heather Winter, Dylan Johnson, and Alan K. Jarmusch!

Haven't heard of MassQL? Check out our blog post here: www.ometalabs.net/resources/ma...

Banner image with breaking news that scientists have discovered the final metabolite.

Guess our job here is done.

Contact — Ometa Labs Get in touch! Drop in for office hours or schedule a meet and greet to discuss your small molecule analysis needs with Ometa's expert team.

Have a burning compound identification question? Drop by our office hours on Tuesdays from 12-1 pm Eastern to discuss with our team.

Sign up here: www.ometalabs.net/contact

Note: if you're an academic, check out the GNPS2 office hours here: wang-bioinformatics-lab.github.io/GNPS2_Docume...

What to look for in metabolomics CROs — Ometa Labs CROs are a great and cost-effective way to run metabolomics experiments, but not every CRO provides the same level of analysis. Learn what questions to ask when considering a metabolomics CRO.

Considering running small molecule analysis through a contract research organization (CRO)? While we're not a CRO, we've helped a lot of people analyze data from CROs. Check out our new blog post on what to consider when using a CRO for metabolomics.

www.ometalabs.net/resources/me...

File Conversion — Ometa Labs Why does mass spectrometry data have so many file formats and which format should I use?

You can also check out our blog post on file formats in mass spectrometry and why open formats are so important here: www.ometalabs.net/resources/fi...

Have opinions about mass spectrometry file formats? Check out the new mzPeak white paper and join the discussion on how to make mass spectrometry data formats open, scalable, and interoperable.

zenodo.org/records/1492...

#massspectrometry #bigdata

A guide to reverse metabolomics—a framework for big data discovery strategy - Nature Protocols In this reverse metabolomics protocol, a tandem mass spectrometry spectrum is used as a search term to probe public metabolomic data. Analysis of the metadata connected with these search results enabl...

Great protocol on reverse metabolomics. An incredible technique if you are generating lead compounds or optimizing production or purification of natural products.

Congrats to the wonderful team of authors!

www.nature.com/articles/s41...

#reversemetabolomics #massspectrometry #discovery #bigdata

Discovery of metabolites prevails amid in-source fragmentation - Nature Metabolism Nature Metabolism - Discovery of metabolites prevails amid in-source fragmentation

Incredibly interesting paper on metabolite discovery and in-source fragmentation.

Congrats to all the authors!

Check it out here: www.nature.com/articles/s42...

#discovery #metabolites #massspectrometry

MS-RT: A Method for Evaluating MS/MS Clustering Performance for Metabolomics Data The clustering of tandem mass spectra (MS/MS) is a crucial computational step to deduplicate repeated acquisitions in data-dependent experiments. This technique is essential in untargeted metabolomics...

Another fascinating paper evaluating MS/MS clustering performance in metabolomics data:

pubs.acs.org/doi/10.1021/...

Spoiler alert: if you'd like to try Falcon clustering, let us know!

Congrats to @mingxunwang.bsky.social, the team at @corteva.bsky.social, and all the other authors!

The International Space Station has a unique and extreme microbial and chemical environment driven by use patterns With long-term space travel and extraterrestrial habitation becoming feasible, understanding how space environmental exposures, microbial communities, and molecular profiles differ from Earth is cruci...

Congrats to all the people who put in tremendous effort to make this study possible. Such a fun project!

www.cell.com/cell/fulltex...

#space #metabolomics #microbes