The study of host specificity has important connections to the question about the origin of SARS-CoV-2 in humans which led to the COVID-19 pandemic—an important open question. There are speculations that bats are a possible origin. Likewise, there are many closely related (corona)viruses, such as SARS, which was found to be transmitted through civets. The study of the different hosts which can be potential carriers and transmitters of deadly viruses to humans is crucial to understanding, mitigating, and preventing current and future pandemics. In coronaviruses, the surface (S) protein, or spike protein, is important in determining host specificity, since it is the point of contact between the virus and the host cell membrane. In this paper, we classify the hosts of over five thousand coronaviruses from their spike protein sequences, segregating them into clusters of distinct hosts among birds, bats, camels, swine, humans, and weasels, to name a few. We propose a feature embedding based on the well-known position weight matrix (PWM), which we call PWM2Vec, and we use it to generate feature vectors from the spike protein sequences of these coronaviruses. While our embedding is inspired by the success of PWMs in biological applications, such as determining protein function and identifying transcription factor binding sites, we are the first (to the best of our knowledge) to use PWMs from viral sequences to generate fixed-length feature vector representations, and use them in the context of host classification. The results on real world data show that when using PWM2Vec, machine learning classifiers are able to perform comparably to the baseline models in terms of predictive performance and runtime—in some cases, the performance is better. We also measure the importance of different amino acids using information gain to show the amino acids which are important for predicting the host of a given coronavirus. Finally, we perform some statistical analyses on these results to show that our embedding is more compact than the embeddings of the baseline models.

Understanding the host-specificity of different families of viruses sheds light on the origin of, e.g., SARS-CoV-2, rabies, and other such zoonotic pathogens in humans. It enables epidemiologists, medical professionals, and policymakers to curb existing epidemics and prevent future ones promptly. In the family Coronaviridae (of which SARS-CoV-2 is a member), it is well-known that the spike protein is the point of contact between the virus and the host cell membrane. On the other hand, the two traditional mammalian orders, Carnivora (carnivores) and Chiroptera (bats) are recognized to be responsible for maintaining and spreading the Rabies Lyssavirus (RABV). We propose Virus2Vec, a feature-vector representation for viral (nucleotide or amino acid) sequences that enable vector-space-based machine learning models to identify viral hosts. Virus2Vec generates numerical feature vectors for unaligned sequences, allowing us to forego the computationally expensive sequence alignment step from the pipeline. Virus2Vec leverages the power of both the \emph{minimizer} and position weight matrix (PWM) to generate compact feature vectors. Using several classifiers, we empirically evaluate Virus2Vec on real-world spike sequences of Coronaviridae and rabies virus sequence data to predict the host (identifying the reservoirs of infection). Our results demonstrate that Virus2Vec outperforms the predictive accuracies of baseline and state-of-the-art methods.

COVID-19 pandemic, is still unknown and is an important open question. There are speculations that bats are a possible origin. Likewise, there are many closely related (corona-) viruses, such as SARS, which was found to be transmitted through civets. The study of the different hosts which can be potential carriers and transmitters of deadly viruses to humans is crucial to understanding, mitigating and preventing current and future pandemics. In coronaviruses, the surface (S) protein, or spike protein, is an important part of determining host specificity since it is the point of contact between the virus and the host cell membrane. In this paper, we classify the hosts of over five thousand coronaviruses from their spike protein sequences, segregating them into clusters of distinct hosts among avians, bats, camels, swines, humans and weasels, to name a few. We propose a feature embedding based on the well-known position-weight matrix (PWM), which we call PWM2Vec, and use to generate feature vectors from the spike protein sequences of these coronaviruses. While our embedding is inspired by the success of PWMs in biological applications such as determining protein function, or identifying transcription factor binding sites, we are the first (to the best of our knowledge) to use PWMs in the context of host classification from viral sequences to generate a fixed-length feature vector representation. The results on the real world data show that in using PWM2Vec, we are able to perform comparably well as compared to baseline models. We also measure the importance of different amino acids using information gain to show the amino acids which are important for predicting the host of a given coronavirus.

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has generated a renewed interest in the larger family of Coronaviridae, which causes a variety of different respiratory infections in a variety of different hosts. Understanding the mechanisms behind the ability of a family of viruses to spill over into different hosts is an ongoing study. In this work, we studied the relationship between specific amino acid sites and the solvent accessibility of the surface (or spike) protein of different Coronaviridae. Since host specificity hinges on the portion(s) of the protein that interfaces with the host cell membrane, there could be a relationship between information gain in specific amino acid sites and solvent accessibility. We found a connection between sites with high information gain and solvent accessibility within several major subgenera of Coronaviridae. Such a connection could be used to study other lesser-known families of viruses, which is desirable because information gain is much easier to compute when the number of sequences is large, as we show. Finally, we produced a visualization of the sequences within each major subgenus and discussed several regions of interest, as well as focused on some pairs of Coronaviridae hosts of interest.

The amount of sequencing data for SARS-CoV-2 is several orders of magnitude larger than any virus. This will continue to grow geometrically for SARS-CoV-2, and other viruses, as many countries heavily finance genomic surveillance efforts. Hence, we need methods for processing large amounts of sequence data to allow for effective yet timely decision-making. Such data will come from heterogeneous sources: aligned, unaligned, or even unassembled raw nucleotide or amino acid sequencing reads pertaining to the whole genome or regions (e.g., spike) of interest. In this work, we propose \emph{ViralVectors}, a compact feature vector generation from virome sequencing data that allows effective downstream analysis. Such generation is based on \emph{minimizers}, a type of lightweight "signature" of a sequence, used traditionally in assembly and read mapping -- to our knowledge, the first use minimizers in this way. We validate our approach on different types of sequencing data: (a) 2.5M SARS-CoV-2 spike sequences (to show scalability); (b) 3K Coronaviridae spike sequences (to show robustness to more genomic variability); and (c) 4K raw WGS reads sets taken from nasal-swab PCR tests (to show the ability to process unassembled reads). Our results show that ViralVectors outperforms current benchmarks in most classification and clustering tasks.