Sebastian Böcker

MSNovelist has appeared in Nature Methods

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Congratulations to Michael “Michele” Stravs from the group of Nicola Zamboni at ETH Zürich: The article “MSNovelist: De novo structure generation from mass spectra” has appeared in Nature Methods, and we are thrilled to be part of this research.

MSNovelist workflow
MSNovelist transforms a MS/MS into a molecular fingerprint via the CSI:FingerID fingerprint prediction, then uses this fingerprint to generate molecular structures. Fig. by Michele Stravs, adapted from the MSNovelist Nature Methods paper.

In short, MSNovelist is a computational method that transforms the tandem mass spectrum of a small molecule into its molecular structure. Full stop. That sounds shocking and surprising, and in fact, I view this as the “final frontier” in small molecule mass spectrometry. It is understood that “certain restrictions apply”, as they say. But Michele has undertaken an huge amount amount of work to clearly show what the method can do and what it cannot; for example, an in-depth evaluation against a method that basically ignores MS/MS data when generating structures. That methods works disturbingly well; but if you think about it for some time, it becomes clear why: I just say, “blockbuster metabolites“. Michele has written a very nice blog post where he explains in much detail what MSNovelist is all about. If I had to recap the method in one sentence, then this is it: MSNovelist gives you a head start for the de novo elucidation of a novel structure.

We will make MSNovelist available through SIRIUS in an upcoming release — hopefully, soon.

ps. Also read the article “Some assembly required” by Corey D. Broeckling.

Full citation: M. A. Stravs, K. Dührkop, S. Böcker, and Nicola Zamboni. MSNovelist: De novo structure generation from mass spectra. Nature Methods, 2022. https://doi.org/10.1038/s41592-022-01486-3

Why we do not use metascores

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…and why you should also be very careful when doing so

Hi all, I (Sebastian) have recorded a talk about metascores which is now available from our YouTube channel at https://www.youtube.com/watch?v=mkfG6-ZqD0s. With “metascores”, I mean scores that are not based on the actual data (or metadata!) but rather on side information such as citation counts or production volumes of metabolites. See below for the distinction between metascores and metadata.

I have been thinking about recording such a talk for several years now. I never did, partly because I hoped that this topic would “go away” without me doing such a video. I was wrong, metascores are still in much use today. The other reason not recording the talk was that the more I thought about metascores, the more problems came into my mind. So, I added more slides to the talk, and then I had to re-record the talk, and so on ad infinitum. I now present six problems in the video; I decided I better record it before a seventh problem pops up.

I want to make clear that there is nothing bad with metascores as long as you are using them for a confined application: That is, you want to identify one particular feature in your LC-MS run, and for that you need some candidate compounds to get things started. If this is what you are after, and the actual identification is performed by an independent method (say, buying a commercial standard and doing a spike-in experiment) then you can generate the sorted list of candidates by any method that suits you; that clearly includes metascores. But as soon as you are doing “untargeted metabolomics” or anything similar to that, and as soon as you are using annotations of an in silico method to derive downstream information, you are in trouble — as explained in the video.

I discuss six problems of metascores in the talk, and I thought I will also shortly discuss them here. But first, let us discuss metascores vs. metadata.

Metascores vs. metadata

I previously had some discussions about metascores, and I have come to believe that some people think highly of metascores because of the connection to metadata. Well, point is, this is merely a misunderstanding. Metascores and metadata have nothing in common but the prefix “meta”. Metadata is data about your data; it is already used by in silico methods, be it the mass accuracy of the measurement or the ion mode. Metascores — at least the ones I am aware of — use side information, information which has nothing to do with the actual experiment you are conducting. See here for details. Side note: Using such side information (priors) has been discussed repeatedly in other fields such as transcriptomics or proteomics, but has been abandoned everywhere else many years ago.

1st problem: Blockbuster metabolites

This is potentially the biggest single issue of metascores: You will annotate the same metabolites again and again. They are simply “so much cooler” than everything else that a method can basically ignore the data. Who will not love to watch another blockbuster movie? And who will not love to annotate another blockbuster metabolite? See here for details.

2nd problem: Evaluation results are misleading

This is not so much a problem of metascores, but one that is caused by the interplay of metascores and the data we use for evaluations. In short, do not trust evaluations of metascores; the data used for evaluating them are basically from blockbuster metabolites. Which metascores will then correctly annotate, because they love to annotate blockbuster metabolites, and only blockbuster metabolites. See here for details.

3rd problem: Obfuscating good search results

When I say that metascore methods can basically ignore the MS/MS data, this is not as good as it may sound. These methods will obfuscate high-quality search results of an in silico method, and make it impossible for you to decide whether or not a particular search result is worth to follow up on. This issue gets dramatic if you use annotations to generate, say, statistics about the sample. In short: Never do any further analysis on annotations when a metascore was in play. See here for details.

4th problem: Why are you using MS/MS anyways?

It turns out that using a metascore, you can actually forget about MS/MS data; in evaluations, this data are no longer needed to reach good annotation rates. Isn’t that great news: We can do untargeted metabolomics and get away with LC-MS data, saving ourselves the troubles of recording MS/MS data at all! A classical win-win situation: Faster measurements and untargeted metabolomics. Citing Leonard Hofstadter: “Our babies will be smart and beautiful.” See here for details.

5th problem: You are not searching where you think you are

This problem makes me nervous, personally. We are basically saying we are searching throughout the whole planet Earth when in fact, we are searching only in our apartment. I doubt that I can get across the implications of doing so; but this is a horror for reproducibility, method disclosure etc. See here for details.

6th problem: Overfitting

But citations are a reasonable feature for compound annotation, right? And, metascores using citation numbers improve search results, right? Doesn’t that mean something? Short answer: No. We can also reach excellent search results with a metascore that is using moonstruck features such as “number of consonants in the PubChem synonyms”. See here for details.

I also have a few suggestions how I would proceed, instead of using a metascore. I am convinced that these suggestions are not the final word; rather, they are meant as a starting point.

Hope this talk helps to clear the perception of this particular computational method. Best regards, Sebastian.

COSMIC has appeared in Nature Biotechnology

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Our article “High-confidence structural annotation of metabolites absent from spectral libraries” has just appeared in Nature Biotechnology. Congrats to Martin and all co-authors!

In short, COSMIC allows you to assign confidence to structure annotations. For every structure annotated by CSI:FingerID, COSMIC provides a confidence score (a number between 0 and 1) that tells you how likely it is that this annotation is correct. This is similar in spirit to what is done in spectral library search: Not only is the cosine score used to decide which candidate best fits to the query spectrum; in addition, we use the cosine of the top-scoring candidate (the hit) to decide whether it is likely correct (say, above 0.8), incorrect (say, below 0.6) or in the “twilight” in-between. If you have been using CSI:FingerID for some time, you might have noticed that finding such thresholds is not possible for the CSI:FingerID score. COSMIC closes this gap and tells you if an annotation is likely correct or incorrect.

Doing so is undoubtedly convenient in practice; but this is not what COSMIC is all about. What we can do now is to sort all hits in a dataset or even a repository with respect to confidence, and then concentrate our downstream analysis on high-confidence annotations. Next, we can replace the “usual” structure databases we search in by a structure database made entirely from hypothetical structures generated by combinatorics, machine learning or in silico enzymatic reactions.

We demonstrate COSMIC’s power by generating a database of hypothetical bile acid structures, combinatorially adding amino acids to bile acid cores, yielding 28,630 plausible bile acid conjugate structures. We then searched query MS/MS data from a mice fecal dataset in this combinatorial database, and used the COSMIC confidence score to distinguish between hits that are likely correct or incorrect. We manually evaluated the top 12 hits and found that 11 annotation (91.6%) were likely correct; two annotations were further confirmed using synthetic standards. All 11 bile acid conjugates are “truly novel”, meaning that we could not find those structures in PubChem or any other structure database (or publication). Whereas reporting 11 novel bile acid conjugates may appear rather cool, we argue it is even cooler that we did this without a biological hypothesis beyond “there might be bile acid conjugates out there which nobody knows about”; and that COSMIC found the top bile acid conjugate annotations in a fully automated manner and in in a matter of hours.

We have also annotated 2,666 LC-MS/MS runs from human samples with molecular structures which are currently absent from HMDB, and for which no MS/MS reference data are available; and finally, 17,414 LC-MS/MS runs with annotations for which no MS/MS reference data are available. We hope that some of them might be of interest to you.

If you have an idea of hypothetical structures, similar to the bile acid conjugates, to be searched against thousands of datasets, please let us know.

COSMIC’s confidence score is available through SIRIUS since version 4.8, download here.

 

Happy 25 million queries, CANOPUS!

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We are fully aware that this post is far less interesting to you than it is to us; but sometimes, proud parents just have to do what proud parents have to do: CANOPUS has passed 25 million queries! Congratulations! Wow, that was fast, the preprint appeared on bioRxiv only 14 months ago.

In this context, we can also report that CSI:FingerID has surpassed 120 million queries. Which basically means we missed the round anniversary. We are bad parents; but kids are sometimes growing so quickly, you turn around and they are past 100 million queries.

Have fun with our tools!

 

Introducing COSMIC to assign confidence to annotations

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We are happy to introduce COSMIC, a tool for that allows you to assign confidence to structure annotations. For every structure annotated by CSI:FingerID, COSMIC provides a confidence score (a number between 0 and 1) that tells you how likely it is that this annotation is correct. This is similar in spirit to what is done in spectral library search: Not only is the cosine score used to decide which candidate best fits to the query spectrum; in addition, we use the cosine of the top-scoring candidate (the hit) to decide whether it is likely correct (say, above 0.8), incorrect (say, below 0.6) or in the “twilight” in-between. If you have been using CSI:FingerID for some time, you might have noticed that finding such thresholds is not possible for the CSI:FingerID score. COSMIC closes this gap and tells you if an annotation is likely correct or incorrect.

Deciding whether a certain CSI:FingerID hit is correct or incorrect, is undoubtedly convenient in practice. But this is not what COSMIC is all about. What we can do now is to sort all hits in a dataset or even a repository with respect to confidence, and then concentrate our downstream analysis on high-confidence annotations. Next, we can replace the “usual” structure databases we search in by a structure database made entirely from hypothetical structures generated by combinatorics, machine learning or in silico enzymatic reactions.

We demonstrate COSMIC’s power by generating a database of hypothetical bile acid structures, combinatorially adding amino acids to bile acid cores, yielding 28,630 plausible bile acid conjugate structures. We then searched query MS/MS data from a mice fecal dataset in this combinatorial database, and used the COSMIC confidence score to distinguish between hits that are likely correct or incorrect. We manually evaluated the top 12 hits and found that 11 annotation (91.6%) were likely correct; two annotations were further confirmed using synthetic standards. All 11 bile acid conjugates are “truly novel”, meaning that we could not find those structures in PubChem or any other structure database (or publication). Whereas reporting 11 novel bile acid conjugates may appear rather cool, we argue it is even cooler that we did this without a biological hypothesis beyond “there might be bile acid conjugates out there which nobody knows about”; and that COSMIC found the top bile acid conjugate annotations in a fully automated manner.

We have also annotated 2,666 LC-MS/MS runs from human samples with molecular structures which are currently absent from HMDB, and for which no MS/MS reference data are available; and finally, 17,414 LC-MS/MS runs with annotations for which no MS/MS reference data are available. We hope that some of them might be of interest to you.

See the COSMIC preprint for details, and the COSMIC web page for further information. Update: COSMIC is now available through SIRIUS 4.8 and above, download here.

                                                                      

 

Video Behind the Scenes: CSI:FingerID

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There is a new video available and it is finally explaining CSI:FingerID in much detail — possibly too much detail, the video is more than 2 hours. Covers everything from general thoughts and considerations about in silico methods and methods evaluation, to the details of molecular fingerprints, FingerID and, finally, CSI:FingerID. I am sorry for the bad audio quality, still using my build-in laptop mic.

 

Classes for the masses: CANOPUS has appeared in Nature Biotechnology

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Our article “Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra” has just appeared in Nature Biotechnology. Congrats to Kai and all co-authors!

In short: CANOPUS is a computational tool for systematic compound class annotation. It uses a deep neural network to predict 2,497 compound classes from fragmentation spectra, including all biologically relevant classes. From the machine learning perspective, the interesting part is that different levels of the neural network are trained using different data (heterogeneous training). CANOPUS explicitly targets compounds for which neither spectral nor structural reference data are available, and even predicts classes completely lacking tandem mass spectrometry training data. In evaluation using reference data, CANOPUS reached very high prediction performance (average accuracy of 99.7% in cross-validation) and outperformed four (rather advanced) baseline methods. We used CANOPUS to investigating the effect of microbial colonization in the mouse digestive system, for analyzing the chemodiversity of different Euphorbia plants, and for the structural elucidation of a novel marine natural product.

CANOPUS is already available to users through SIRIUS 4.5, which was released last Thursday. See also the designated CANOPUS page. A view-only version of the article is available here.

Full citation: K. Dührkop, L.-F. Nothias, M. Fleischauer, R. Reher, M. Ludwig, M. A. Hoffmann, D. Petras, W. H. Gerwick, J. Rousu, P. C. Dorrestein, and S. Böcker. Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra. Nat Biotechnol, 2020. https://doi.org/10.1038/s41587-020-0740-8

 

Qemistree has appeared in Nature Chemical Biology

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Congratulations to Anupriya Tripathi from the group of Pieter Dorrestein: The article “Chemically informed analyses of metabolomics mass spectrometry data with Qemistree” has appeared in Nature Chemical Biology, and we are happy to be part of this research.

In short, Qemistree is a data exploration strategy based on the hierarchical organization of molecular fingerprints predicted from fragmentation spectra. Qemistree allows mass spectrometry data to be represented in the context of sample metadata and chemical ontologies.

Full citation: A. Tripathi, Y. Vázquez-Baeza, J. M. Gauglitz, M. Wang, K. Dührkop, M. Nothias-Esposito, D. D. Acharya, M. Ernst, J. J. J. van der Hooft, Q. Zhu, D. McDonald, A. D. Brejnrod, A. Gonzalez, J. Handelsman, M. Fleischauer, M. Ludwig, S. Böcker, L.-F. Nothias, R. Knight, and P. C. Dorrestein. Chemically informed analyses of metabolomics mass spectrometry data with Qemistree. Nat Chem Biol, 2020.

 

Lehre im Wintersemester 2020/21

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Auch im Wintersemester hat uns Corona noch im Griff; deshalb werden die meisten Lehrveranstaltungen online erfolgen. Hier ein paar Details, was Sie erwartet (Achtung, diese news ist eine sticky note; wir werden sie aktualisieren, wenn es weitere Informationen gibt):

  • NEU: Das Seminar Beruf und Karriere (ASQ) findet als Blockveranstaltung in der Woche vom 22. bis 26. März statt. Das Seminar ist online und live (Zoom-Veranstaltung). Details folgen, Anmeldung über Friedolin ist bereits möglich.
  • Einführung in die Bioinformatik I/1: Die Vorlesung macht Peter Dittrich; die Video-Dateien werden zum Download bereitgestellt und Sie können sich diese anhören/ansehen, wann es Ihnen passt. Wöchentlich am Dienstag von 10:15 bis 11:45 ist das Tutorium bei Sebastian Böcker; auch das wird online angeboten, ist aber live (Zoom-Veranstaltung). Die beiden Übungen sind parallel wöchentlich am Mittwoch von 14:15 bis 15:45. Das sind Präsenzveranstaltungen, und sie finden im Hörsaal 1 des Abbeanum und im Seminarraum 104 in der August-Bebel-Str. 4 statt. (Edit: Es sieht aktuell so aus, dass wir die Übungen als Präsenzveranstaltungen durchführen können.) Übungsleiter sind Marcus Ludwig und Emanuel Barth. Die Aufteilung auf die beiden Gruppen können wir im ersten Tutorium vornehmen. Die Veranstaltung startet mit dem Tutorium am Dienstag 3. November.
  • Algorithmische Massenspektrometrie: VL und Tutorium bei Sebastian Böcker. Die VL wird als Video-Dateien zum Download bereitgestellt, das Tutorium ist online aber live (Zoom-Veranstaltung), wöchentlich am Montag von 12:3o bis 14:oo. Die Übung ist wöchentlich am Donnerstag 12-14 Uhr, online aber live (Zoom-Veranstaltung), Übungsleiter ist Kai Dührkop. Die Veranstaltung startet mit dem Tutorium am Montag 2. November.
  • Currents in Bioinformatics: Das Seminar findet wöchentlich Dienstags 16:15 bis 17:45 statt (online aber live, Zoom-Veranstaltung). Ansprechpartner ist Fleming Kretschmer. Regelmäßige Teilnahme ist zwingend erforderlich. Wir lesen und besprechen hier aktuelle Forschungs-Paper. Die Veranstaltung startet am Dienstag 3. November.
  • Datamining und Sequenzanalyse: Die Veranstaltung wird von Markus Fleischauer gehalten und findet Mo 10:15-11:45h und  Fr 12:30-14:00h statt. Wir werden auch diese Veranstaltung online durchführen, sofern alle Studierenden einen geeigneten Computer zur Durchführung der Programmieraufgaben zur Verfügung haben. Ein Computer ist für das Praktikum geeignet, wenn er diese Anforderungen erfüllt. Alle für das Praktikum benötigte Software ist für Linux, Mac und Windows verfügbar und wird während des Praktikums gemeinsam installiert. Sollte jemand keinen geeigneten Computer organisieren können, bitte umgehend bei Markus Fleischauer melden. Wir werden Zoom verwenden. Der Link wird rechtzeitig mitgeteilt. Alle Informationen zur Veranstaltung werden hier zu finden sein. Start ist am Montag 02. November um 10:15 Uhr.

Bei individuellen Problemen und Fragen wenden Sie sich bitte via Email an Peter Dittrich (Studiengangsverantwortlicher) oder Sebastian Böcker. Sie können auch individuelle Gespräche via Zoom vereinbaren.

FSU-Disclaimer zum Vorlesungsmaterial, insbesondere zu den Videos mit den Vorlesungen:

  • In unseren Veranstaltungen und ihrer Aufzeichnung wird ggf. urheberrechtlich geschütztes Material verwandt. Eine Nutzung, etwa durch Verbreitung oder Veröffentlichung dieses Materials, ist untersagt und kann die Geltendmachung von Unterlassungs- und Schadensersatzansprüchen zur Folge haben.

 

ZODIAC has appeared in Nature Machine Intelligence

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Our article “Database-independent molecular formula annotation using Gibbs sampling through ZODIAC” has just appeared in Nature Machine Intelligence. Congrats to Marcus and all co-authors!

In short: Annotating the molecular formula of a small molecule is the first step towards its structural elucidation but remains highly challenging, particularly for “large compounds” above 500 Daltons. ZODIAC is a network-based algorithm for the de novo annotation (no database needed) of molecular formulas, and processes complete experimental LC-MS/MS runs. (No metabolite is an island.) In comparison to SIRIUS, previously best-of-class for this task, ZODIAC reduces the error rate of false annotations roughly to the half. And sometimes, much more…

If you have problems accessing the paper: Here is a read-only version. 

ZODIAC is already available to users through SIRIUS 4.4. See also the designated ZODIAC page.

Full citation: M. Ludwig, L.-F. Nothias, K. Dührkop, I. Koester, M. Fleischauer, M.A. Hoffmann, D. Petras, F. Vargas, M. Morsy, L. Aluwihare, P.C. Dorrestein, and S. Böcker. Database-independent molecular formula annotation using Gibbs sampling through ZODIAC. Nat Mach Intell 2:629–641, 2020.

Feature-Based Molecular Networking appeared in Nature Methods

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Congratulations to Louis-Félix Nothias from the group of Pieter Dorrestein: The article “Feature-based molecular networking in the GNPS analysis environment” has appeared in Nature Methods, and we are happy to be part of this research. (We are lacking behind a little bit with our news.)

In short, FBMN introduces chromatography separation into the molecular networking workflow of GNPS; features with similar mass (and potentially similar MS/MS) but different retention time are now treated separately. See the article for details.

Full citation: L.-F. Nothias, D. Petras, R. Schmid, K. Dührkop, J. Rainer, A. Sarvepalli, I. Protsyuk, M. Ernst, H. Tsugawa, M. Fleischauer, F. Aicheler, A.A. Aksenov, O. Alka, P.-M. Allard, A. Barsch, X. Cachet, A.M. Caraballo-Rodriguez, R.R. Da Silva, T. Dang, N. Garg, J.M. Gauglitz, A. Gurevich, G. Isaac, A.K. Jarmusch, Z. Kameník, K.B. Kang, N. Kessler, I. Koester, A. Korf, A. Le Gouellec, M. Ludwig, C. Martin H., L.-I. McCall, J. McSayles, S.W. Meyer, H. Mohimani, M. Morsy, O. Moyne, S. Neumann, H. Neuweger, N.H. Nguyen, M. Nothias-Esposito, J. Paolini, V.V. Phelan, T. Pluskal, R.A. Quinn, S. Rogers, B. Shrestha, A. Tripathi, J.J.J. van der Hooft, F. Vargas, K.C. Weldon, M. Witting, H. Yang, Z. Zhang, F. Zubeil, O. Kohlbacher, S. Böcker, T. Alexandrov, N. Bandeira, M. Wang, and P.C. Dorrestein. Feature-based molecular networking in the GNPS analysis environment. Nat Methods 17(9):905–908, 2020.

Introducing CANOPUS for comprehensive compound class annotation

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We are happy to introduce CANOPUS, a tool for the comprehensive annotation of compound classes from MS/MS data (certain restrictions apply, see below). In principle, CANOPUS is doing something similar as CSI:FingerID: Whereas CSI:FingerID can tell you what substructures are part of the query compound, CANOPUS does so for compound classes. The differences between both tasks are subtle but have massive consequences. See this preprint on the details of this difference, how CANOPUS works, how good it works etc.

At present, CANOPUS predicts 1270 compound classes. In more detail, CANOPUS predicts ClassyFire compound classes. ClassyFire is not the first but, to the best of our knowledge, by far the most comprehensive approach to assign classes solely from structure. (This last point is key, as this allows us to assign thousands of classes for millions of molecular structures.) Please have a look there if you use CANOPUS: Certain compound class definitions may be not what you expect. For example, we found that many phytosteroids are classified as bile acids in ClassyFire. While the biochemical origin of both classes is very different, they are structural very similar and, therefore, represented by the same class in the ClassyFire ontology.

You can download, install and use CANOPUS through SIRIUS 4.4. You will notice a new tab where you can access, for each compound, all compound classes it does or does not belong to (and, how sure we are about that). Fancier visualizations (see the preprint) will be made available with upcoming releases.

ps. Clearly, CANOPUS is comprehensive only within the limits of the LC-MS/MS technology: If a compound does not ionize, if no fragmentation spectrum is recorded in Data Dependent Acquisition, if a compound does not show any fragmentation, if multiple compounds are fragmented in a single spectrum etc, then CANOPUS cannot help you. We don’t do magic. Also, CANOPUS is limited by the available (structure and MS/MS) training data; but several years of thinking have been invested to get the most out of it.

Introducing ZODIAC for improved molecular formula annotations

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We are happy to introduce ZODIAC, a tool for the comprehensive annotation of molecular formulas for complete LC-MS/MS runs. SIRIUS 4 is currently best-of-class for this task (as far as we know); but ZODIAC can do better. Different from SIRIUS which considers one compound at a time, ZODIAC considers a complete dataset, assuming that all compounds are somehow related (usually through biotransformations). See the preprint for evaluation and method details.

ZODIAC is about de novo annotations, meaning that we can assign molecular formulas for novel compounds currently absent from any structure database. ZODIAC takes into account “uncommon” elements, as in C24H47BrNO8P or C15H30ClIO5; both examples are indeed novel molecular formulas annotated by ZODIAC (and verified by us). Enter those molecular formulas into the PubChem search and see what you get back. (Fun fact: the first query now returns two entries created Jan 2020 based on our annotations.)

You can download, install and use ZODIAC through SIRIUS 4.4. Results of ZODIAC are simply displayed in the molecular formula tab, if you choose to run it. You should definitely use ZODIAC if you want to run CANOPUS: Assigning molecular classes to novel compounds implies that some of the molecular formulas may be novel, too; and you do not want provide CANOPUS a wrong molecular formula.

The ZODIAC score is displayed in the overview tab.

ps. Sorry for tweeting early, WordPress sometimes has a mind of its own.

SIRIUS 4.4 released

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We are happy to announce that SIRIUS 4.4 is finally released. (Unfortunately, the MacOS version will have to wait a few more days.) There have been numerous changes and improvements, only few of which can be mentioned here.

Probably the biggest change is that SIRIUS 4.4 now reads mzML files (“centroided” data) and processes complete LC-MS/MS datasets. You can use ProteoWizard to transform your dataset to mzML. This does not only make things easier for you; it also allows SIRIUS to extract isotope patterns and adduct information more thoroughly from the MS1 data. SIRIUS 4.4 also supports multi-run datasets and aligns runs.

If you are using the graphical user interface (GUI) you no longer have to care about installing (the correct version of) Java. It is part of the installed SIRIUS software.

SIRIUS 4.4 uses the same project space for the command-line (CLI) and the GUI version, allowing you to use the SIRIUS GUI to browse through results computed with the CLI. The GUI also allows you to save your project and reload it later, including all previously computed results. Finally, you can export summary CSV and mzTab-M files for downstream analysis.

CSI:FingerID also had some updates:

  • Additional large molecular substructures: Have a look at the Fingerprint tab in the SIRIUS GUI, filter for large substructures.
  • Standardization of molecular structures (mesomerism, charge etc) through PubChem. This does not only improve identification statistics by a few percentage points, but also gets rid of certain cases where CSI:FingerID was doing “strange things”. Unfortunately, PubChem keeps changing the standardization without giving big notice, so some issues remain; but the current situation is definitely better than no standardization.

More stuff:

  • There is currently no version for MacOS; we are sorry. Somehow, MacOS does not like our multithreading. At present, we do not have access to a Mac for debugging, thanks to Corona.
  • Please report bugs using the SIRIUS GitHub repository or . There will be numerous such bugs, as SIRIUS 4.4 again carries major improvements and transformations under the hood. Help us to make SIRIUS better.
  • To allow for a smooth transition, you can continue to use SIRIUS 4.0.1 and the corresponding CSI:FingerID web service for a couple of weeks.
  • SIRIUS 4.4 integrates ZODIAC and CANOPUS, see the separate news.
  • passatutto is integrated into SIRIUS 4.4, allowing you to generate your own spectral library decoy database for FDR estimation.
  • We have included a beautiful interactive fragmentation tree viewer.
  • There may be a few more releases of SIRIUS 4.4.x that ship those things which are done in principle.
  • Finally, we have not reported the number of CSI:FingerID queries for some time, so here we go: There have been 47 million CSI:FingerID queries. (Plus a few million we lost through a little scripting bug. Our bad.) That is roughly one query every 1.5 seconds since we reported one million queries in Feb 2018.

 

Hiccup of FSU computer network

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Yesterday (27 April 2020) our university computer network experienced some issues and was unavailable for several hours. Not unexpectedly, this also resulted in the unavailability of the CSI:FingerID web service, website etc. As usual, computer problems cause more computer problems: It looks like today (28 April 2020) we still have certain issues restarting the CSI:FingerID workers. That is hopefully resolved soon. We apologize for any inconvenience.

 

SIRIUS 4.4 beta released

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Some of you may have noticed that yesterday, April 17, the SIRIUS 4.4 beta has been released. This update is huge so we are particularly careful not to break too many things. (We will definitely break some things so please report bugs using the SIRIUS GitHub repository or .) Some facts of what you can expect:

  • The official SIRIUS 4.4 release will happen in a few days.
  • Even after SIRIUS 4.4 has been officially deployed, you can continue to use SIRIUS 4.0.1 and the corresponding CSI:FingerID web service. We hope that this allows for a smooth transition.
  • SIRIUS 4.4 integrates ZODIAC for better molecular formulas.
  • SIRIUS 4.4 integrates CANOPUS for compound class assignments.
  • SIRIUS 4.4 now reads mzML files (“centroided” data) and processes complete LC-MS/MS datasets.
  • CSI:FingerID had some massive updates, including more and larger molecular properties and standardization of molecular structures.
  • SIRIUS 4.4 also supports multi-run datasets and aligns runs.
  • SIRIUS 4.4 uses the same project space for the command-line and the user interface version, allowing you to use the SIRIUS GUI to browse through results computed with the CLI.
  • passatutto is integrated into SIRIUS 4.4, allowing you to generate your own spectral library decoy database for FDR estimation.
  • If you wonder why we jump from version 4.0.1 to 4.4: There have been several internal releases in between.
  • A word of warning: Many features and changes have accumulated and there will be a few more releases (4.4.x) until the quiver is empty. For example, the structure database will change again as we have massive issues with the way PubChem handles structure standardization.