Search bioRxiv⌕ Search

Biology subjects

Amgarten, D.

Publications and source records attributed to Amgarten, D..

2 recordsLinked to original sources

Genomic foundation model embeddings encode higher-order viral genome architecture beyond sequence composition: a benchmark of Evo 2

Genomic foundation models such as Evo 2 are increasingly applied to microbial genomics, yet how well their representations capture viral genome organisation, and how reliably they generate viral sequence, remain poorly characterised. We present a reproducible benchmark of Evo 2 on viral genomes. Using a pre-registered RefSeq viral corpus (19,429 genomes, organised by Baltimore class and host domain), we evaluated three axes: linear probes decoding Baltimore class, host domain and viral family from mean-pooled embeddings; ridge-regression probes recovering genomic features, including higher-order architectural properties such as gene density, coding fraction and gene overlap; and generative completion of fragmented genomes, scored on a leakage-safe set of eukaryote-infecting viruses (excluded from Evo 2s training corpus by design) against a bacteriophage comparator. All probes used cross-validation with sequence-identity-clustered folds, benchmarked against both a GC-and-length control and a 6-mer composition representation. From its optimal intermediate layer, the 20B embedding classified Baltimore class at 0.96 accuracy and host domain at 0.99, exceeding both baselines; for viral family, however, 6-mer composition (0.89) matched the embedding (0.91. Most informatively, the embedding decoded coding fraction, gene density and gene overlap (R{superscript 2} = 0.61, 0.77 and 0.64) far beyond 6-mer composition (0.10, 0.38 and 0.27), evidencing genuine encoding of genome architecture rather than nucleotide composition (p < 0.001). Performance scaled with model size. In generation, perplexity was lower for bacteriophages (1.18 bits/nt) than for held-out eukaryotic viruses (1.80). Evo 2 encodes functional viral genome architecture beyond composition, while taxonomic and generative behaviour partly reflect composition and training exposure.

bioinformatics↗

vHULK, a new tool for bacteriophage host prediction based on annotated genomic features and deep neural networks

The experimental determination of a bacteriophage host is a laborious procedure. For this reason, there is a pressing need for reliable computational predictions of bacteriophage hosts in phage research in general and in phage therapy in particular. Here, we present a new program called vHULK for phage host prediction based on 9,504 phage genome features. These features take into account alignment significance scores between predicted-protein sequences in the phage genomes and a curated database of viral protein families. The features were fed to a deep neural network, and four distinct models were trained to predict 61 different host genera and 52 host species. In random controlled test sets, the program obtained 99% and 98% accuracy values at the genus and species levels, respectively. On a validation dataset with 2,178 phage genomes, mean accuracies were 82% and 52% at the genus and species levels, respectively. When compared against other phage host prediction programs on the same validation dataset, vHULK achieved substantially better performance, therefore demonstrating that the program is an advance on the state-of-art in phage host prediction. vHULK is freely available at https://github.com/LaboratorioBioinformatica/vHULK.

bioinformatics↗