2026

Arnaiz del Pozo C, Sanchis-Lopez C, Huerta-Cepas J
bioRxiv doi:10.64898/2026.03.27.714410 bioRxiv (2026). DOI

demultiplexing and basecalling pipeline for Nanopore sequencing runs with dual-indexed Illumina-style barcodes, packaged as a reproducible Nextflow workflow.

Deng Z, Sanchis-López C, Hernández-Plaza A, Davín AA, Huerta-Cepas J
Mol Biol Evol 43(2):msag028, 2026 DOI

TreeProfiler is a command-line tool that annotates any phylogenetic tree with metadata (ecology, taxonomy, phenotypes) and lets researchers visualise and query patterns across thousands of tips at once.

Hernández-Plaza A, Deng Z, Robledo-Yagüe F, Szklarczyk D, von Mering C, Bork P, Huerta-Cepas J
Nucleic Acids Res 54(D1):D402-D408, 2026 DOI

eggNOG v7 expands the gold-standard database of orthologous genes to cover 12,000+ species, adding phylogeny-aware functional predictions that help scientists interpret what newly sequenced genes do.

2025

Gutierrez-Manso L, Devesa-Aranguren I, Conesa CM, Monteoliva-García G, González-Sáyer S, Lozano-Enguita A, Blasio F, Ugena L, Nolasco J, Vázquez-Mora A, Levy CCB, Otero EA, Fernández-Calvo P, Moreno-Risueno MÁ, Petrik I, Pěnčík A, Reguera M, González-Bodí S, Huerta-Cepas J, Sacristán S, Del Pozo JC, Cabrera J
bioRxiv 2025.12.05.692050, 2025 DOI

The soil fungus Penicillium melinii boosts root growth in crops by producing specific metabolites; the study maps the molecular mechanisms behind this plant-growth promotion.

Sebé-Pedrós A, Tanay A, Lawniczak MKN, Arendt D, Aerts S, Archibald J, Arnone MI, Blaxter M, Cleves P, Coelho SM, Dias M, Dunn C, Elek A, Frazer J, Gabaldón T, Gillis J, Grau-Bové X, Guigó R, Hobert O, Huerta-Cepas J, Irimia M, Klein A, Lewin H, Lowe CJ, Marlow H, Musser JM, Nagy LG, Najle SR, Pachter L, Paez S, Papatheodorou I, Passalacqua MJ, Rajewsky N, Rhee SY, Richards TA, Sauka-Spengler T, Saunders LM, Seuntjens E, Solana J, Song Y, Technau U, Wang B
Nature 645(8082):877-885, 2025 DOI

A global atlas mapping gene expression across the full tree of life at the single-cell level, revealing universal and lineage-specific cell-type programmes from microbes to animals.

Sanchis-Lopez C, Santamaria-Hernando S, Cantalapiedra CP, Pokorny L, Gonzalez-Recio O, Sunagawa S, Lopez-Solanilla E, Huerta-Cepas J
bioRxiv doi:10.1101/2025.06.24.661292 bioRxiv (2025). DOI

A deep dive into environmental DNA databases reveals that chemoreceptor genes—bacterial sensors for chemical signals—are far more diverse and widespread in rare microbial communities than previously thought.

González-Bodí S, Huerta-Cepas J
Methods Mol Biol 2899:309-338, 2025 DOI

A step-by-step protocol for RNA-seq differential expression analysis using the Galaxy computational platform, accessible without programming skills.

2024

Díaz-García C, Moreno E, Talavera-Rodríguez A, Martín-Fernández L, González-Bodí S, Martín-Pedraza L, Pérez-Molina JA, Dronda F, Gosalbes MJ, Luna L, Vivancos MJ, Huerta-Cepas J, Moreno S, Serrano-Villar S
Microbiome 12(1):214, 2024 DOI

Faecal microbiota transplantation (FMT) in HIV patients reshapes the gut immune environment by changing which proteins are produced, pointing to microbiome-based strategies to reduce chronic inflammation.

Langschied F, Bordin N, Cosentino S, Fuentes-Palacios D, Glover N, Hiller M, Hu Y, Huerta-Cepas J, Coelho LP, Iwasaki W, Majidian S, Manzano-Morales S, Persson E, Richards TA, Gabaldón T, Sonnhammer E, Thomas PD, Dessimoz C, Ebersberger I
Genome Biol Evol 16(10):evae224, 2024 DOI

A perspective on how the surge in biodiversity genomics—sequencing organisms across the full tree of life—is transforming our ability to detect and study orthologous genes at an unprecedented scale.

Santos-Júnior CD, Torres MDT, Duan Y, Rodríguez Del Río Á, Schmidt TSB, Chong H, Fullam A, Kuhn M, Zhu C, Houseman A, Somborski J, Vines A, Zhao XM, Bork P, Huerta-Cepas J, de la Fuente-Nunez C, Coelho LP
Cell 187(14):3761-3778.e16, 2024 DOI

Machine learning scans millions of metagenome sequences and discovers thousands of previously unknown antimicrobial peptides with activity against drug-resistant bacteria.

Baker BA, Gutiérrez-Preciado A, Rodríguez Del Río Á, McCarthy CGP, López-García P, Huerta-Cepas J, Susko E, Roger AJ, Eme L, Moreira D
Nat Microbiol 9(4):964-975, 2024 DOI

A new large-scale phylogeny of salt-loving archaea shows that extreme halophily evolved independently multiple times, and identifies dozens of new lineages in hypersaline environments.

Dmitrijeva M, Tackmann J, Matias Rodrigues JF, Huerta-Cepas J, Coelho LP, von Mering C
Nat Ecol Evol 8(5):986-998, 2024 DOI

Analysing nearly one million prokaryotic genomes, the study maps how ecological pressures and evolutionary history jointly shape genome size, gene content, and metabolic diversity.

2023

Rodríguez Del Río Á, Giner-Lamia J, Cantalapiedra CP, Botas J, Deng Z, Hernández-Plaza A, Munar-Palmer M, Santamaría-Hernando S, Rodríguez-Herva JJ, Ruscheweyh HJ, Paoli L, Schmidt TSB, Sunagawa S, Bork P, López-Solanilla E, Coelho LP, Huerta-Cepas J
Nature 626(7998):377-384, 2024 DOI

Tens of millions of genes in environmental metagenomes lack any functional annotation. This study shows many of these 'unknown' genes are ancient, conserved, and likely encode novel essential functions.

Manzano-Morales S, Liu Y, González-Bodí S, Huerta-Cepas J, Iranzo J
Genome Biol 24(1):250, 2023 DOI

Different criteria used to cluster genes into ortholog groups give different results; the study benchmarks them systematically and shows that no single method is universally best.

Santos-Júnior CD, Der Torossian Torres M, Duan Y, Del Río ÁR, Schmidt TSB, Chong H, Fullam A, Kuhn M, Zhu C, Houseman A, Somborski J, Vines A, Zhao XM, Bork P, Huerta-Cepas J, de la Fuente-Nunez C, Coelho LP
bioRxiv 2023.08.31.555663, 2023 DOI

A computational pipeline screens environmental microbiome data for natural antibiotic compounds, identifying promising leads against resistant pathogens.

Huch S, Nersisyan L, Ropat M, Barrett D, Wu M, Wang J, Valeriano VD, Vardazaryan N, Huerta-Cepas J, Wei W, Du J, Steinmetz LM, Engstrand L, Pelechano V
Nat Microbiol 8(6):1123-1136, 2023 DOI

A comprehensive atlas of mRNA translation and decay rates across hundreds of bacterial species, revealing universal regulatory principles and species-specific adaptations.

Fullam A, Letunic I, Schmidt TSB, Ducarmon QR, Karcher N, Khedkar S, Kuhn M, Larralde M, Maistrenko OM, Malfertheiner L, Milanese A, Rodrigues JFM, Sanchis-López C, Schudoma C, Szklarczyk D, Sunagawa S, Zeller G, Huerta-Cepas J, von Mering C, Bork P, Mende DR
Nucleic Acids Res 51(D1):D760-D766, 2023 DOI

proGenomes3 provides nearly one million consistently annotated prokaryotic genomes with curated taxonomy and habitat labels, enabling large-scale comparative genomics.

Hernández-Plaza A, Szklarczyk D, Botas J, Cantalapiedra CP, Giner-Lamia J, Mende DR, Kirsch R, Rattei T, Letunic I, Jensen LJ, Bork P, von Mering C, Huerta-Cepas J
Nucleic Acids Res 51(D1):D389-D394, 2023 DOI

eggNOG 6.0 updates the comprehensive orthology database to cover 12,535 organisms with improved functional annotations, enabling comparative genomics at scale.

2022

Gong X, Del Río ÁR, Xu L, Chen Z, Langwig MV, Su L, Sun M, Huerta-Cepas J, De Anda V, Baker BJ
Nat Commun 13(1):7516, 2022 DOI

Discovery of new bacterial phyla within the FCB superphylum using metagenome-assembled genomes, expanding our understanding of microbial diversity.

Shaffer JP, Nothias LF, Thompson LR, Sanders JG, Salido RA, Couvillion SP, Brejnrod AD, Lejzerowicz F, Haiminen N, Huang S, Lutz HL, Zhu Q, Martino C, Morton JT, Karthikeyan S, Nothias-Esposito M, Dührkop K, Böcker S, Kim HW, Aksenov AA, Bittremieux W, Minich JJ, Marotz C, Bryant MM, Sanders K, Schwartz T, Humphrey G, Vásquez-Baeza Y, Tripathi A, Parida L, Carrieri AP, Beck KL, Das P, González A, McDonald D, Ladau J, Karst SM, Albertsen M, Ackermann G, DeReus J, Thomas T, Petras D, Shade A, Stegen J, Song SJ, Metz TO, Swafford AD, Dorrestein PC, Jansson JK, Gilbert JA, Knight R
Nat Microbiol 7(12):2128-2150, 2022 DOI

A multi-omics study of Earth's diverse microbiomes finds conserved metabolic functions and microbial markers shared across very different environments.

Botas J, Rodríguez Del Río Á, Giner-Lamia J, Huerta-Cepas J
Nucleic Acids Res 50(W1):W352-W357, 2022 DOI

GeCoViz is a web tool to visualise the genomic neighbourhood of prokaryotic genes, helping researchers understand gene function through their genomic context.

Deng Z, Botas J, Cantalapiedra CP, Hernández-Plaza A, Burguet-Castell J, Huerta-Cepas J
Nucleic Acids Res 50(W1):W577-W582, 2022 DOI

PhyloCloud is an online platform to store, visualise, and share large phylogenomic trees and their associated metadata.

2021

Coelho LP, Alves R, Del Río ÁR, Myers PN, Cantalapiedra CP, Giner-Lamia J, Schmidt TS, Mende DR, Orakov A, Letunic I, Hildebrand F, Van Rossum T, Forslund SK, Khedkar S, Maistrenko OM, Pan S, Jia L, Ferretti P, Sunagawa S, Zhao XM, Nielsen HB, Huerta-Cepas J, Bork P
Nature 601(7892):252-256, 2022 DOI

Analysing thousands of prokaryotic genomes, this study maps the global biogeography of microbial genes and shows that geography and ecology both shape gene distributions.

Cantalapiedra CP, Hernández-Plaza A, Letunic I, Bork P, Huerta-Cepas J
Mol Biol Evol 38(12):5825-5829, 2021 DOI

eggNOG-mapper v2 greatly expands the functional annotation pipeline, adding domain predictions, GO terms, and KEGG pathway assignments for any protein or gene set.

Musser JM, Schippers KJ, Nickel M, Mizzon G, Kohn AB, Pape C, Ronchi P, Papadopoulos N, Tarashansky AJ, Hammel JU, Wolf F, Liang C, Hernández-Plaza A, Cantalapiedra CP, Achim K, Schieber NL, Pan L, Ruperti F, Francis WR, Vargas S, Kling S, Renkert M, Polikarpov M, Bourenkov G, Feuda R, Gaspar I, Burkhardt P, Wang B, Bork P, Beck M, Schneider TR, Kreshuk A, Wörheide G, Huerta-Cepas J, Schwab Y, Moroz LL, Arendt D
Science 374(6568):717-723, 2021 DOI

Single-cell sequencing of sponges—among the earliest animals—reveals the origins of nervous system cell types and sheds light on animal evolution.

Sanchis-López C, Cerna-Vargas JP, Santamaría-Hernando S, Ramos C, Krell T, Rodríguez-Palenzuela P, López-Solanilla E, Huerta-Cepas J, Rodríguez-Herva JJ
mSystems 6(5):e0095121, 2021 DOI

A survey of chemoreceptor repertoires in plant-associated bacteria shows that microbial sensory capacity is highly tuned to the plant environment.

Linard B, Ebersberger I, McGlynn SE, Glover N, Mochizuki T, Patricio M, Lecompte O, Nevers Y, Thomas PD, Gabaldón T, Sonnhammer E, Dessimoz C, Uchiyama I
Mol Biol Evol 38(8):3033-3045, 2021 DOI

A 10-year retrospective on the Quest for Orthologs community effort, summarising achievements, remaining challenges, and future directions in orthology research.

2020

Altenhoff AM, Garrayo-Ventas J, Cosentino S, Emms D, Glover NM, Hernández-Plaza A, Nevers Y, Sundesha V, Szklarczyk D, Fernández JM, Codó L, Gelpi JL, Huerta-Cepas J, Iwasaki W, Kelly S, Lecompte O, Muffato M, Martin MJ, Capella-Gutierrez S, Thomas PD, Sonnhammer E, Dessimoz C
Nucleic Acids Res 48(W1):W538-W545, 2020 DOI

The Quest for Orthologs community benchmarks 15 orthology methods on reference datasets, providing a consensus guide for researchers choosing tools.

Maistrenko OM, Mende DR, Luetge M, Hildebrand F, Schmidt TSB, Li SS, Rodrigues JFM, von Mering C, Pedro Coelho L, Huerta-Cepas J, Sunagawa S, Bork P
ISME J 14(5):1247-1259, 2020 DOI

A large-scale comparison disentangles how environmental conditions versus evolutionary history drive differences in prokaryotic genome content and metabolic potential.

Mende DR, Letunic I, Maistrenko OM, Schmidt TSB, Milanese A, Paoli L, Hernández-Plaza A, Orakov AN, Forslund SK, Sunagawa S, Zeller G, Huerta-Cepas J, Coelho LP, Bork P
Nucleic Acids Res 48(D1):D621-D625, 2020 DOI

proGenomes2 improves the database of annotated prokaryotic genomes with better taxonomy, habitat labels, and consistency checks across one million entries.

2019

Salazar G, Paoli L, Alberti A, Huerta-Cepas J, Ruscheweyh HJ, Cuenca M, Field CM, Coelho LP, Cruaud C, Engelen S, Gregory AC, Labadie K, Marec C, Pelletier E, Royo-Llonch M, Roux S, Sánchez P, Uehara H, Zayed AA, Zeller G, Carmichael M, Dimier C, Ferland J, Kandels S, Picheral M, Pisarev S, Poulain J, Acinas SG, Babin M, Bork P, Bowler C, de Vargas C, Guidi L, Hingamp P, Iudicone D, Karp-Boss L, Karsenti E, Ogata H, Pesant S, Speich S, Sullivan MB, Wincker P, Sunagawa S
Cell 179(5):1068-1083.e21, 2019 DOI

Analysing global ocean metagenomes over time, the study separates gene-expression changes (within species) from community turnover (species replacement) as drivers of ecosystem-level shifts.

Glover N, Dessimoz C, Ebersberger I, Forslund SK, Gabaldón T, Huerta-Cepas J, Martin MJ, Muffato M, Patricio M, Pereira C, da Silva AS, Wang Y, Sonnhammer E, Thomas PD
Mol Biol Evol 36(10):2157-2164, 2019 DOI

A review of the advances and biological applications enabled by accurate orthology prediction tools over the past decade.

Coelho LP, Alves R, Monteiro P, Huerta-Cepas J, Freitas AT, Bork P
Microbiome 7(1):84, 2019 DOI

NG-meta-profiler uses NGLess—a domain-specific language for NGS data—to process metagenomes faster and more reproducibly than general-purpose tools.

Milanese A, Mende DR, Paoli L, Salazar G, Ruscheweyh HJ, Cuenca M, Hingamp P, Alves R, Costea PI, Coelho LP, Schmidt TSB, Almeida A, Mitchell AL, Finn RD, Huerta-Cepas J, Bork P, Zeller G, Sunagawa S
Nat Commun 10(1):1014, 2019 DOI

mOTUs2 profiles the abundance of microbial species from shotgun metagenome data using marker genes, enabling culture-independent community comparisons.

Hildebrand F, Moitinho-Silva L, Blasche S, Jahn MT, Gossmann TI, Huerta-Cepas J, Hercog R, Luetge M, Bahram M, Pryszlak A, Alves RJ, Waszak SM, Zhu A, Ye L, Costea PI, Aalvink S, Belzer C, Forslund SK, Sunagawa S, Hentschel U, Merten C, Patil KR, Benes V, Bork P
Gut 68(10):1781-1790, 2019 DOI

Treatment with broad-spectrum antibiotics can allow a single rare bacterial order to take over the gut, demonstrating how antibiotics disrupt microbial balance.

Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV
Nucleic Acids Res 47(D1):D607-D613, 2019 DOI

STRING v11 updates the comprehensive protein interaction database to cover more organisms and interaction evidence types, enabling network-based functional analysis.

Huerta-Cepas J, Szklarczyk D, Heller D, Hernández-Plaza A, Forslund SK, Cook H, Mende DR, Letunic I, Rattei T, Jensen LJ, von Mering C, Bork P
Nucleic Acids Res 47(D1):D309-D314, 2019 DOI

eggNOG 5.0 builds a hierarchical database of orthologous genes across 4,445 organisms, with functional annotations at each taxonomic level.

2018

Kampinga HH, Andreasson C, Barducci A, Cheetham ME, Cyr D, Emanuelsson C, Genevaux P, Gestwicki JE, Goloubinoff P, Huerta-Cepas J, Kirstein J, Liberek K, Mayer MP, Nagata K, Nillegoda NB, Pulido P, Ramos C, De Los Rios P, Rospert S, Rosenzweig R, Sahi C, Taipale M, Tomiczek B, Ushioda R, Young JC, Zimmermann R, Zylicz A, Zylicz M, Craig EA, Marszalek J
Cell Stress Chaperones 24(1):7-15, 2019 DOI

A comprehensive review of J-domain proteins (co-chaperones), covering their structure, evolutionary history, and roles in protein folding and cellular stress.

Bahram M, Hildebrand F, Forslund SK, Anderson JL, Soudzilovskaia NA, Bodegom PM, Bengtsson-Palme J, Anslan S, Coelho LP, Harend H, Huerta-Cepas J, Medema MH, Maltz MR, Mundra S, Olsson PA, Pent M, Põlme S, Sunagawa S, Ryberg M, Tedersoo L, Bork P
Nature 560(7717):233-237, 2018 DOI

Shotgun sequencing and analysis of global topsoil samples reveals an enormous diversity of microbial life and its role in nutrient cycling.

Forslund K, Pereira C, Capella-Gutierrez S, da Silva AS, Altenhoff A, Huerta-Cepas J, Muffato M, Patricio M, Vandepoele K, Ebersberger I, Blake J, Fernández Breis JT, Boeckmann B, Gabaldón T, Sonnhammer E, Dessimoz C, Lewis S
Bioinformatics 34(2):323-329, 2018 DOI

A perspective on how the mosaic nature of microbial genomes—driven by horizontal gene transfer—complicates orthology inference and what strategies help.

2017

Costea PI, Coelho LP, Sunagawa S, Munch R, Huerta-Cepas J, Forslund K, Hildebrand F, Kushugulova A, Zeller G, Bork P
Mol Syst Biol 13(12):960, 2017 DOI

Analysis of metagenomic data from the global Human Microbiome Project identifies consistent subspecies within major gut bacterial species.

Huerta-Cepas J, Forslund K, Coelho LP, Szklarczyk D, Jensen LJ, von Mering C, Bork P
Mol Biol Evol 34(8):2115-2122, 2017 DOI

eggNOG-mapper performs rapid genome-wide functional annotation by assigning orthologs from the eggNOG database and propagating their functional terms.

Czech L, Huerta-Cepas J, Stamatakis A
Mol Biol Evol 34(6):1535-1542, 2017 DOI

A critical analysis of how support values (bootstrap, posterior probability) are displayed and interpreted in phylogenetic tree-viewing software.

Jouhten P, Huerta-Cepas J, Bork P, Patil KR
Metab Eng 40:1-4, 2017 DOI

Metabolic engineering of a 'anchor reaction' strategy to maintain stable performance in microbial cell factories.

Mende DR, Letunic I, Huerta-Cepas J, Li SS, Forslund K, Sunagawa S, Bork P
Nucleic Acids Res 45(D1):D529-D534, 2017 DOI

proGenomes provides a curated collection of prokaryotic genomes with consistent functional and taxonomic annotations for comparative genomics.

2016

Kultima JR, Coelho LP, Forslund K, Huerta-Cepas J, Li SS, Driessen M, Voigt AY, Zeller G, Sunagawa S, Bork P
Bioinformatics 32(16):2520-2523, 2016 DOI

MOCAT2 is a pipeline for assembling, annotating, and profiling microbial genes from shotgun metagenome data.

Huerta-Cepas J, Serra F, Bork P
Mol Biol Evol 33(6):1635-1638, 2016 DOI

ETE 3 is a Python toolkit for phylogenetic tree handling, offering analysis and publication-quality visualisation of large trees and their metadata.

Baa-Puyoulet P, Parisot N, Febvay G, Huerta-Cepas J, Vellozo AF, Gabaldón T, Calevro F, Charles H, Colella S
Database (Oxford) 2016:baw081, 2016 DOI

ArthropodaCyc provides metabolic pathway databases for arthropod genomes, built on the CycADS automated annotation system.

Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojärvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P
Science 352(6285):586-589, 2016 DOI

After faecal microbiota transplantation, donor bacteria can stably coexist with the recipient's own bacteria for years, demonstrating lasting microbiome engraftment.

Altenhoff AM, Boeckmann B, Capella-Gutierrez S, Dalquen DA, DeLuca T, Forslund K, Huerta-Cepas J, Linard B, Pereira C, Pryszcz LP, Schreiber F, da Silva AS, Szklarczyk D, Train CM, Bork P, Lecompte O, von Mering C, Xenarios I, Sjölander K, Jensen LJ, Martin MJ, Muffato M, Gabaldón T, Lewis SE, Thomas PD, Sonnhammer E, Dessimoz C
Nat Methods 13(5):425-430, 2016 DOI

A standardised benchmarking framework for orthology methods, providing reference datasets and metrics to compare tools on equal footing.

Huerta-Cepas J, Szklarczyk D, Forslund K, Cook H, Heller D, Walter MC, Rattei T, Mende DR, Sunagawa S, Kuhn M, Jensen LJ, von Mering C, Bork P
Nucleic Acids Res 44(D1):D286-D293, 2016 DOI

eggNOG 4.5 restructures the orthology database into a hierarchical framework with improved functional coverage and updated annotations.