SignalP 6.0 achieves signal peptide prediction across all types using protein language models

Teufel, Felix; Jja, Armenteros; Ar, Johansen; Mh, Gislason; Si, Pihl; Tsirigos, Konstantinos D.; Winther, Ole; Brunak, Søren; Heijne, Gunnar von; Nielsen, Henrik

doi:10.1101/2021.06.09.447770

Cited by 26 publications

(25 citation statements)

References 35 publications

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“…Presence of the signal peptides in the analyzed proteins was assessed with the SignalP version 5.0 and further confirmed with newly released SignalP 6.0 [100,101].…”

Section: Bioinformatic Analysismentioning

confidence: 99%

Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis

Banaś

Bocian-Ostrzycka

Dunin-Horkawicz

et al. 2021

IJMS

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The bacterial proteins of the Dsb family catalyze the formation of disulfide bridges between cysteine residues that stabilize protein structures and ensure their proper functioning. Here, we report the detailed analysis of the Dsb pathway of Campylobacter jejuni. The oxidizing Dsb system of this pathogen is unique because it consists of two monomeric DsbAs (DsbA1 and DsbA2) and one dimeric bifunctional protein (C8J_1298). Previously, we showed that DsbA1 and C8J_1298 are redundant. Here, we unraveled the interaction between the two monomeric DsbAs by in vitro and in vivo experiments and by solving their structures and found that both monomeric DsbAs are dispensable proteins. Their structures confirmed that they are homologs of EcDsbL. The slight differences seen in the surface charge of the proteins do not affect the interaction with their redox partner. Comparative proteomics showed that several respiratory proteins, as well as periplasmic transport proteins, are targets of the Dsb system. Some of these, both donors and electron acceptors, are essential elements of the C. jejuni respiratory process under oxygen-limiting conditions in the host intestine. The data presented provide detailed information on the function of the C. jejuni Dsb system, identifying it as a potential target for novel antibacterial molecules.

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“…Presence of the signal peptides in the analyzed proteins was assessed with the SignalP version 5.0 and further confirmed with newly released SignalP 6.0 [100,101].…”

Section: Bioinformatic Analysismentioning

confidence: 99%

Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis

Banaś

Bocian-Ostrzycka

Dunin-Horkawicz

et al. 2021

IJMS

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“…Pretrained transformer protein MLMs contain structural information [Rao et al, 2019, Rives et al, 2021, Chowdhury et al, 2021], encode evolutionary trajectories [Hie et al, 2022a, 2021], are zero-shot predictors of mutation fitness effects [Meier et al, 2021], improve out-of-domain generalization on protein engineering datasets [Dallago et al, 2021], and suggest improved sequences for engineering [Hie et al, 2022b]. Protein MLMs are now incorporated into the latest machine-learning methods for detecting signal peptides [Teufel et al, 2021] and predicting intracellular localization[Thumuluri et al, 2022].…”

Section: Introductionmentioning

confidence: 99%

Convolutions are competitive with transformers for protein sequence pretraining

Yang

Fusi

2022

Preprint

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Pretrained protein sequence language models largely rely on the transformer architecture. However, transformer run-time and memory requirements scale quadrat-ically with sequence length. We investigate the potential of a convolution-based architecture for protein sequence masked language model pretraining and subsequent finetuning. CNNs are competitive on the pretraining task with transformers across several orders of magnitude in parameter size while scaling linearly with sequence length. More importantly, CNNs are competitive with and occasionally superior to transformers across an extensive set of downstream evaluations, including structure prediction, zero-shot mutation effect prediction, and out-of-domain generalization. We also demonstrate strong performance on sequences longer than the positional embeddings allowed in the current state-of-the-art transformer protein masked language models. Finally, we close with a call to disentangle the effects of pretraining task and model architecture when studying pretrained protein sequence models.

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“…Protein domains and families were identified using pfam_scan.pl (v1.6; http://ftp.ebi.ac.uk/pub/databases/Pfam/Tools/) on Pfam database (release 34.0; Mistry et al, 2021). Additional annotations were carried out as follows: carbohydrates active enzymes were determined using dbCAN2 (v2.0.11; Zhang et al, 2018); secondary metabolites detection via antiSMASH (v6.0; Blin et al, 2021); fungal effectors were predicted using EffectorP (v3.0; Sperschneider & Dodds, 2022) on amino acid sequences which passed the signal peptide prediction via signalP (v6.0; Teufel et al, 2021); and genes related to pathogen-host interaction were determined via PHI-base (v4.11; Urban et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…Detailed information such as sequencing platforms, library kits used and sequence accession number for each sample can be found in Pfam database (release 34.0; Mistry et al, 2021). Additional annotations were carried out as follows: carbohydrates active enzymes were determined using dbCAN2 (v2.0.11; ; secondary metabolites detection via antiSMASH (v6.0; Blin et al, 2021); fungal effectors were predicted using EffectorP (v3.0; Sperschneider & Dodds, 2022) on amino acid sequences which passed the signal peptide prediction via signalP (v6.0; Teufel et al, 2021);…”

Section: Nucleic Acids Isolation Genome and Transcriptome Sequencingmentioning

confidence: 99%

Fusarium solanispecies complex genomes reveal bases of compartmentalisation and animal pathogenesis

Hoh

Lee

Wada

et al. 2022

Preprint

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The Fusarium solani species complex (FSSC) comprises fungal pathogens responsible for mortality in a diverse range of animals and plants, but their genome diversity and transcriptome responses in animal pathogenicity remain to be elucidated. We sequenced and compared six chromosome-level FSSC clade 3 genomes of aquatic animal and plant host origins and revealed a spectrum of conservation patterns in chromosomes categorised into three compartments: core, fast-core (FC), and lineage-specific (LS). Each chromosome type varied in structural architectures, with FC and LS chromosomes containing significantly higher proportions of repetitive elements and methylation levels than core chromosomes, with genes exhibiting higher dN/dS and enriched in functions related to pathogenicity and niche expansion. Mesosynteny were detected between FC chromosomes of Fusarium genomes, indicating that these chromosomes were present in a common ancestor that predated FSSC species. These findings provide evidence that genome compartmentalisation was the outcome of multi-speed evolution amongst FSSC chromosomes. We further demonstrated that F. falciforme and F. keratoplasticum are opportunistic pathogens by inoculating Pelodiscus sinensis eggs and identified differentially expressed genes also associated with plant pathogenicity. These included the most upregulated genes encoding the CFEM (Common in Fungal Extracellular Membrane) domain. The study establishes genomic resources and an animal model for fungal pathogens of trans-kingdom hosts.

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SignalP 6.0 achieves signal peptide prediction across all types using protein language models

Cited by 26 publications

References 35 publications

Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis

Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis

Convolutions are competitive with transformers for protein sequence pretraining

Fusarium solanispecies complex genomes reveal bases of compartmentalisation and animal pathogenesis

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