Evidence map›Paper›PMID 42649115›Full record

ArticleBriefings in bioinformatics2026

FireProtASR 2.0: evolution-guided Design of Protein Ancestors and Successors with phylogenetics and machine learning.

Pavel Kohout, David Lacko, Milos Musil, Simeon Borko, Martin Stepanek, Jan Velecky, Petr Kabourek, Rayyan Tariq Khan, Monika Rosinska, Jiri Damborsky and 2 more

Abstract read
In one paragraph

Article in Briefings in bioinformatics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Pavel KohoutLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
David LackoLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.ORCID 0009-0007-0332-9193
Milos MusilLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Simeon BorkoLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Martin StepanekLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Jan VeleckyLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.ORCID 0000-0002-5316-6990
Petr KabourekLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Rayyan Tariq KhanLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Monika RosinskaLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.
Jiri DamborskyLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.ORCID 0000-0002-7848-8216
Stanislav MazurenkoLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.ORCID 0000-0003-3659-4819
David BednarLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.ORCID 0000-0002-6803-0340

Funding

European Union Centre of Excellence CLARA 101136607European Union's Horizon 2020 research and innovation programme 857560 CETOCOENTechnology Agency of the Czech Republic TN02000122/001N
6 · The paper itself

Abstract

Evolution-guided protein design remains one of the most effective strategies for engineering proteins with enhanced stability, activity, or specificity. To make these approaches more accessible, we previously developed FireProtASR-a fully automated pipeline for ancestral sequence reconstruction (ASR). Here, we present FireProtASR 2.0, a significantly enhanced version that extends the design space beyond ancestral inference by integrating a successor sequence predictor (SSP) and a generative model based on variational autoencoders (VAEs). These new modules enable both 'prospective' and 'retrospective' evolutionary design strategies. The SSP module predicts likely future mutations based on site-wise evolutionary trends, and the method was previously validated through in silico benchmarks, demonstrating improvements in thermostability and activity. The VAE module captures global evolutionary constraints in a low-dimensional latent space, from which novel functional ancestral-like variants can be sampled. The VAE-based design strategy was previously validated experimentally on the haloalkane dehalogenase family, yielding variants with enhanced thermostability while maintaining catalytic activity. Both these modules are newly available in FireProtASR in a fully automated pipeline, guiding the users via an interactive graphical user interface. With expanded functionality, modernized user interface, and a more robust backend, FireProtASR 2.0 provides a comprehensive, accessible, and fully automated platform for evolutionary-based protein engineering (https://loschmidt.chemi.muni.cz/fireprotasr/).

Indexed as

Evolution, MolecularMachine LearningPhylogenyProtein EngineeringProteinsSoftwareAutoencoderComputational BiologyProteinsancestral sequence reconstructionevolutionary modelingmachine learningprotein designsuccessor sequence predictionvariational autoencoders

Identifiers

PMID42649115
PMCPMC13518065

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.