BACKGROUND: Emerging pathogens are a growing threat, but large data collections and approaches for predicting the risk associated with novel agents are limited to bacteria and viruses. Pathogenic fungi, which also pose a constant threat to public health, remain understudied. Relevant data remain comparatively scarce and scattered among many different sources, hindering the development of sequencing-based detection workflows for novel fungal pathogens. No prediction method working for agents across all three groups is available, even though the cause of an infection is often difficult to identify from symptoms alone. RESULTS: We present a curated collection of fungal host range data, comprising records on human, animal and plant pathogens, as well as other plant-associated fungi, linked to publicly available genomes. We show that it can be used to predict the pathogenic potential of novel fungal species directly from DNA sequences with either sequence homology or deep learning. We develop learned, numerical representations of the collected genomes and visualize the landscape of fungal pathogenicity. Finally, we train multi-class models predicting if next-generation sequencing reads originate from novel fungal, bacterial or viral threats. CONCLUSIONS: The neural networks trained using our data collection enable accurate detection of novel fungal pathogens. A curated set of over 1400 genomes with host and pathogenicity metadata supports training of machine-learning models and sequence comparison, not limited to the pathogen detection task. AVAILABILITY AND IMPLEMENTATION: The data, models and code are hosted at https://zenodo.org/record/5846345, https://zenodo.org/record/5711877 and https://gitlab.com/dacs-hpi/deepac. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of genomic surveillance to understand the evolution of the virus, to monitor the viral population, and plan epidemiological responses. Detailed analysis, easy visualization and intuitive filtering of the latest viral sequences are powerful for this purpose. We present CovRadar, a tool for genomic surveillance of the SARS-CoV-2 Spike protein. CovRadar consists of an analytical pipeline and a web application that enable the analysis and visualization of hundreds of thousand sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants and consensus and finally presents the results in an interactive app, making accessing and reporting simple, flexible and fast. AVAILABILITY AND IMPLEMENTATION: CovRadar is freely accessible at https://covradar.net, its open-source code is available at https://gitlab.com/dacs-hpi/covradar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Novel pathogens evolve quickly and may emerge rapidly, causing dangerous outbreaks or even global pandemics. Next-generation sequencing is the state of the art in open-view pathogen detection, and one of the few methods available at the earliest stages of an epidemic, even when the biological threat is unknown. Analyzing the samples as the sequencer is running can greatly reduce the turnaround time, but existing tools rely on close matches to lists of known pathogens and perform poorly on novel species. Machine learning approaches can predict if single reads originate from more distant, unknown pathogens but require relatively long input sequences and processed data from a finished sequencing run. Incomplete sequences contain less information, leading to a trade-off between sequencing time and detection accuracy. Using a workflow for real-time pathogenic potential prediction, we investigate which subsequences already allow accurate inference. We train deep neural networks to classify Illumina and Nanopore reads and integrate the models with HiLive2, a real-time Illumina mapper. This approach outperforms alternatives based on machine learning and sequence alignment on simulated and real data, including SARS-CoV-2 sequencing runs. After just 50 Illumina cycles, we observe an 80-fold sensitivity increase compared to real-time mapping. The first 250 bp of Nanopore reads, corresponding to 0.5 s of sequencing time, are enough to yield predictions more accurate than mapping the finished long reads. The approach could also be used for screening synthetic sequences against biosecurity threats.

MOTIVATION: We expect novel pathogens to arise due to their fast-paced evolution, and new species to be discovered thanks to advances in DNA sequencing and metagenomics. Moreover, recent developments in synthetic biology raise concerns that some strains of bacteria could be modified for malicious purposes. Traditional approaches to open-view pathogen detection depend on databases of known organisms, which limits their performance on unknown, unrecognized and unmapped sequences. In contrast, machine learning methods can infer pathogenic phenotypes from single NGS reads, even though the biological context is unavailable. RESULTS: We present DeePaC, a Deep Learning Approach to Pathogenicity Classification. It includes a flexible framework allowing easy evaluation of neural architectures with reverse-complement parameter sharing. We show that convolutional neural networks and LSTMs outperform the state-of-the-art based on both sequence homology and machine learning. Combining a deep learning approach with integrating the predictions for both mates in a read pair results in cutting the error rate almost in half in comparison to the previous state-of-the-art. AVAILABILITY AND IMPLEMENTATION: The code and the models are available at: https://gitlab.com/rki_bioinformatics/DeePaC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.