Reads2Vec: Efficient Embedding of Raw High-Throughput Sequencing Reads Data.

The massive amount of genomic data appearing for SARS-CoV-2 since the beginning of the COVID-19 pandemic has challenged traditional methods for studying its dynamics. As a result, new methods such as Pangolin, which can scale to the millions of samples of SARS-CoV-2 currently available, have appeared. Such a tool is tailored to take as input assembled, aligned, and curated full-length sequences, such as those found in the GISAID database. As high-throughput sequencing technologies continue to advance, such assembly, alignment, and curation may become a bottleneck, creating a need for methods that can process raw sequencing reads directly. In this article, we propose Reads2Vec, an alignment-free embedding approach that can generate a fixed-length feature vector representation directly from the raw sequencing reads without requiring assembly. Furthermore, since such an embedding is a numerical representation, it may be applied to highly optimized classification and clustering algorithms. Experiments on simulated data show that our proposed embedding obtains better classification results and better clustering properties contrary to existing alignment-free baselines. In a study on real data, we show that alignment-free embeddings have better clustering properties than the Pangolin tool and that the spike region of the SARS-CoV-2 genome heavily informs the alignment-free clusterings, which is consistent with current biological knowledge of SARS-CoV-2.

Benchmarking machine learning robustness in Covid-19 genome sequence classification.

The rapid spread of the COVID-19 pandemic has resulted in an unprecedented amount of sequence data of the SARS-CoV-2 genome-millions of sequences and counting. This amount of data, while being orders of magnitude beyond the capacity of traditional approaches to understanding the diversity, dynamics, and evolution of viruses, is nonetheless a rich resource for machine learning (ML) approaches as alternatives for extracting such important information from these data. It is of hence utmost importance to design a framework for testing and benchmarking the robustness of these ML models. This paper makes the first effort (to our knowledge) to benchmark the robustness of ML models by simulating biological sequences with errors. In this paper, we introduce several ways to perturb SARS-CoV-2 genome sequences to mimic the error profiles of common sequencing platforms such as Illumina and PacBio. We show from experiments on a wide array of ML models that some simulation-based approaches with different perturbation budgets are more robust (and accurate) than others for specific embedding methods to certain noise simulations on the input sequences. Our benchmarking framework may assist researchers in properly assessing different ML models and help them understand the behavior of the SARS-CoV-2 virus or avoid possible future pandemics.

Characterizing SARS-CoV-2 Spike Sequences Based on Geographical Location.

With the rapid spread of COVID-19 worldwide, viral genomic data are available in the order of millions of sequences on public databases such as GISAID. This Big Data creates a unique opportunity for analysis toward the research of effective vaccine development for current pandemics, and avoiding or mitigating future pandemics. One piece of information that comes with every such viral sequence is the geographical location where it was collected-the patterns found between viral variants and geographical location surely being an important part of this analysis. One major challenge that researchers face is processing such huge, highly dimensional data to obtain useful insights as quickly as possible. Most of the existing methods face scalability issues when dealing with the magnitude of such data. In this article, we propose an approach that first computes a numerical representation of the spike protein sequence of SARS-CoV-2 using k-mers (substrings) and then uses several machine learning models to classify the sequences based on geographical location. We show that our proposed model significantly outperforms the baselines. We also show the importance of different amino acids in the spike sequences by computing the information gain corresponding to the true class labels.

Efficient Approximate Kernel Based Spike Sequence Classification.

Machine learning (ML) models, such as SVM, for tasks like classification and clustering of sequences, require a definition of distance/similarity between pairs of sequences. Several methods have been proposed to compute the similarity between sequences, such as the exact approach that counts the number of matches between k-mers (sub-sequences of length k) and an approximate approach that estimates pairwise similarity scores. Although exact methods yield better classification performance, they pose high computational costs, limiting their applicability to a small number of sequences. The approximate algorithms are proven to be more scalable and perform comparably to (sometimes better than) the exact methods - they are designed in a "general" way to deal with different types of sequences (e.g., music, protein, etc.). Although general applicability is a desired property of an algorithm, it is not the case in all scenarios. For example, in the current COVID-19 (coronavirus) pandemic, there is a need for an approach that can deal specifically with the coronavirus. To this end, we propose a series of ways to improve the performance of the approximate kernel (using minimizers and information gain) in order to enhance its predictive performance pm coronavirus sequences. More specifically, we improve the quality of the approximate kernel using domain knowledge (computed using information gain) and efficient preprocessing (using minimizers computation) to classify coronavirus spike protein sequences corresponding to different variants (e.g., Alpha, Beta, Gamma). We report results using different classification and clustering algorithms and evaluate their performance using multiple evaluation metrics. Using two datasets, we show that our proposed method helps improve the kernel's performance compared to the baseline and state-of-the-art approaches in the healthcare domain.

Efficient analysis of COVID-19 clinical data using machine learning models.

Because of the rapid spread of COVID-19 to almost every part of the globe, huge volumes of data and case studies have been made available, providing researchers with a unique opportunity to find trends and make discoveries like never before by leveraging such big data. This data is of many different varieties and can be of different levels of veracity, e.g., precise, imprecise, uncertain, and missing, making it challenging to extract meaningful information from such data. Yet, efficient analyses of this continuously growing and evolving COVID-19 data is crucial to inform - often in real-time - the relevant measures needed for controlling, mitigating, and ultimately avoiding viral spread. Applying machine learning-based algorithms to this big data is a natural approach to take to this aim since they can quickly scale to such data and extract the relevant information in the presence of variety and different levels of veracity. This is important for COVID-19 and potential future pandemics in general. In this paper, we design a straightforward encoding of clinical data (on categorical attributes) into a fixed-length feature vector representation and then propose a model that first performs efficient feature selection from such representation. We apply this approach to two clinical datasets of the COVID-19 patients and then apply different machine learning algorithms downstream for classification purposes. We show that with the efficient feature selection algorithm, we can achieve a prediction accuracy of more than 90% in most cases. We also computed the importance of different attributes in the dataset using information gain. This can help the policymakers focus on only certain attributes to study this disease rather than focusing on multiple random factors that may not be very informative to patient outcomes.

PWM2Vec: An Efficient Embedding Approach for Viral Host Specification from Coronavirus Spike Sequences.

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.

Robust Representation and Efficient Feature Selection Allows for Effective Clustering of SARS-CoV-2 Variants

The widespread availability of large amounts of genomic data on the SARS-CoV-2 virus, as a result of the COVID-19 pandemic, has created an opportunity for researchers to analyze the disease at a level of detail, unlike any virus before it. On the one hand, this will help biologists, policymakers, and other authorities to make timely and appropriate decisions to control the spread of the coronavirus. On the other hand, such studies will help to more effectively deal with any possible future pandemic. Since the SARS-CoV-2 virus contains different variants, each of them having different mutations, performing any analysis on such data becomes a difficult task, given the size of the data. It is well known that much of the variation in the SARS-CoV-2 genome happens disproportionately in the spike region of the genome sequence—the relatively short region which codes for the spike protein(s). In this paper, we propose a robust feature-vector representation of biological sequences that, when combined with the appropriate feature selection method, allows different downstream clustering approaches to perform well on a variety of different measures. We use such proposed approach with an array of clustering techniques to cluster spike protein sequences in order to study the behavior of different known variants that are increasing at a very high rate throughout the world. We use a k-mers based approach first to generate a fixed-length feature vector representation of the spike sequences. We then show that we can efficiently and effectively cluster the spike sequences based on the different variants with the appropriate feature selection. Using a publicly available set of SARS-CoV-2 spike sequences, we perform clustering of these sequences using both hard and soft clustering methods and show that, with our feature selection methods, we can achieve higher F1 scores for the clusters and also better clustering quality metrics compared to baselines.