Murray Patterson

Mansoor Ahmed, Huirong Chai, Haoxin Wang et al.

Antibodies neutralize foreign antigens by binding to specific surface regions called epitopes. Computational epitope prediction is critical for understanding immune recognition and guiding antibody engineering. However, existing methods face three fundamental challenges: antibody-aware models encode each chain independently and combine them only at a late stage, failing to capture co-dependent structural features that define binding interfaces, whereas severe class imbalance and scarcity of known antibody-antigen complexes render standard training objectives ineffective. We propose EpiFormer, a general encoder-decoder framework that addresses these challenges jointly. Our key design principle is interleaved cross-attention within GNN encoding layers, enabling bidirectional antigen-antibody information flow throughout representation learning rather than only at the output. This early-fusion principle is backbone-agnostic, providing consistent gains across GNN architectures from simple GCNs to equivariant models. We further show that sparsity-aware objectives are effective when paired with early-fusion architectures for the epitope prediction task. EpiFormer improves over the previous best method by over 40% in F1 score on standard benchmarks, demonstrating generalizability and cross-dataset transferability. Notably, EpiFormer discovers known biological principles as emergent behaviors of end-to-end training, where the learned cross-attention gates favor antigen-to-antibody information flow, consistent with the asymmetric roles of the two chains at the binding interface, and the model's preference for geometric over evolutionary features aligns with the established finding that epitope residues are not evolutionarily conserved. The source code is available at: https://github.com/mansoor181/epiformer.git

Sarwan Ali, Bikram Sahoo, Muhammad Asad Khan et al.

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.

Mansoor Ahmed, Murray Patterson

Antibody design methods condition on antigen structure to generate complementarity-determining regions (CDR), yet a systematic evaluation of baseline methods reveals that they largely ignore the antigen input. We identify three failure modes that explain this behavior. Antigen blindness arises because models derive predictions from antibody framework context rather than antigen information, producing nearly identical CDRs regardless of the target. Vocabulary collapse reduces predicted amino acids to three to five per position, far below the ground truth distribution in native sequences. Moreover, any model trained with standard per-position cross-entropy converges to the positional marginal distribution, making it provably unable to produce antigen-specific sequence predictions. We propose a novel encoder-decoder architecture called AgForce, that uses a graph neural network (GNN) as the encoder and specialized decoders for sequence-structure co-design. Specifically, we apply framework dropout, gated bottlenecks, and hyperbolic cross attention that prevent the antibody shortcut path. In the decoder, a Mixture Density Network (MDN) sequence head with Potts-like pairwise coupling and annealed Multiple Choice Learning (aMCL) replaces the cross-entropy objective with a multi-component distribution whose optimal solution differs from the positional marginal. An antigen cycle consistency head routes gradients through the sequence decoder, forcing predicted distributions to encode antigen identity. AgForce achieves the best binding quality and sequence recovery simultaneously on the CHIMERA-Bench dataset, improving amino acid recovery by 8% over the strongest sequence baseline while surpassing the baselines across all interface metrics, and nearly doubling the effective vocabulary of GNN methods. The source code is available at: https://github.com/mansoor181/ag-force.git

Mansoor Ahmed, Nadeem Taj, Imdad Ullah Khan et al.

Computational antibody design has seen rapid methodological progress, with dozens of deep generative methods proposed in the past three years, yet the field lacks a standardized benchmark for fair comparison and model development. These methods are evaluated on different SAbDab snapshots, non-overlapping test sets, and incompatible metrics, and the literature fragments the design problem into numerous sub-tasks with no common definition. We introduce \textsc{Chimera-Bench} (\textbf{C}DR \textbf{M}odeling with \textbf{E}pitope-guided \textbf{R}edesign), a unified benchmark built around a single canonical task: \emph{epitope-conditioned CDR sequence-structure co-design}. \textsc{Chimera-Bench} provides (1) a curated, deduplicated dataset of \textbf{2,922} antibody-antigen complexes with epitope and paratope annotations; (2) three biologically motivated splits testing generalization to unseen epitopes, unseen antigen folds, and prospective temporal targets; and (3) a comprehensive evaluation protocol with five metric groups including novel epitope-specificity measures. We benchmark representative methods spanning different generative paradigms and report results across all splits. \textsc{Chimera-Bench} is the largest dataset of its kind for the antibody design problem, allowing the community to develop and test novel methods and evaluate their generalizability. The source code and data are available at: https://github.com/mansoor181/chimera-bench.git

Usama Sardar, Sarwan Ali, Muhammad Sohaib Ayub et al.

Nanobodies (Nb) are monomeric heavy-chain fragments derived from heavy-chain only antibodies naturally found in Camelids and Sharks. Their considerably small size (~3-4 nm; 13 kDa) and favorable biophysical properties make them attractive targets for recombinant production. Furthermore, their unique ability to bind selectively to specific antigens, such as toxins, chemicals, bacteria, and viruses, makes them powerful tools in cell biology, structural biology, medical diagnostics, and future therapeutic agents in treating cancer and other serious illnesses. However, a critical challenge in nanobodies production is the unavailability of nanobodies for a majority of antigens. Although some computational methods have been proposed to screen potential nanobodies for given target antigens, their practical application is highly restricted due to their reliance on 3D structures. Moreover, predicting nanobodyantigen interactions (binding) is a time-consuming and labor-intensive task. This study aims to develop a machine-learning method to predict Nanobody-Antigen binding solely based on the sequence data. We curated a comprehensive dataset of Nanobody-Antigen binding and nonbinding data and devised an embedding method based on gapped k-mers to predict binding based only on sequences of nanobody and antigen. Our approach achieves up to 90% accuracy in binding prediction and is significantly more efficient compared to the widely-used computational docking technique.

Sarwan Ali, Bikram Sahoo, Alexander Zelikovskiy et al.

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 are more robust (and accurate) than others for specific embedding methods to certain adversarial attacks to 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.

Prakash Chourasia, Sarwan Ali, Simone Ciccolella et al.

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 which can process raw sequencing reads directly. In this paper, 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.

Prakash Chourasia, Sarwan Ali, Murray Patterson

The t-distributed stochastic neighbor embedding (t- SNE) is a method for interpreting high dimensional (HD) data by mapping each point to a low dimensional (LD) space (usually two-dimensional). It seeks to retain the structure of the data. An important component of the t-SNE algorithm is the initialization procedure, which begins with the random initialization of an LD vector. Points in this initial vector are then updated to minimize the loss function (the KL divergence) iteratively using gradient descent. This leads comparable points to attract one another while pushing dissimilar points apart. We believe that, by default, these algorithms should employ some form of informative initialization. Another essential component of the t-SNE is using a kernel matrix, a similarity matrix comprising the pairwise distances among the sequences. For t-SNE-based visualization, the Gaussian kernel is employed by default in the literature. However, we show that kernel selection can also play a crucial role in the performance of t-SNE. In this work, we assess the performance of t-SNE with various alternative initialization methods and kernels, using four different sets, out of which three are biological sequences (nucleotide, protein, etc.) datasets obtained from various sources, such as the well-known GISAID database for sequences of the SARS- CoV-2 virus. We perform subjective and objective assessments of these alternatives. We use the resulting t-SNE plots and k- ary neighborhood agreement (k-ANA) to evaluate and compare the proposed methods with the baselines. We show that by using different techniques, such as informed initialization and kernel matrix selection, that t-SNE performs significantly better. Moreover, we show that t-SNE also takes fewer iterations to converge faster with more intelligent initialization.

Prakash Chourasia, Taslim Murad, Zahra Tayebi et al.

This paper presents a federated learning (FL) approach to train an AI model for SARS-Cov-2 variant classification. We analyze the SARS-CoV-2 spike sequences in a distributed way, without data sharing, to detect different variants of this rapidly mutating coronavirus. Our method maintains the confidentiality of local data (that could be stored in different locations) yet allows us to reliably detect and identify different known and unknown variants of the novel coronavirus SARS-CoV-2. Using the proposed approach, we achieve an overall accuracy of $93\%$ on the coronavirus variant identification task. We also provide details regarding how the proposed model follows the main laws of federated learning, such as Laws of data ownership, data privacy, model aggregation, and model heterogeneity. Since the proposed model is distributed, it could scale on ``Big Data'' easily. We plan to use this proof-of-concept to implement a privacy-preserving pandemic response strategy.

Taslim Murad, Sarwan Ali, Murray Patterson

Biological sequence analysis is an essential step toward building a deeper understanding of the underlying functions, structures, and behaviors of the sequences. It can help in identifying the characteristics of the associated organisms, like viruses, etc., and building prevention mechanisms to eradicate their spread and impact, as viruses are known to cause epidemics that can become pandemics globally. New tools for biological sequence analysis are provided by machine learning (ML) technologies to effectively analyze the functions and structures of the sequences. However, these ML-based methods undergo challenges with data imbalance, generally associated with biological sequence datasets, which hinders their performance. Although various strategies are present to address this issue, like the SMOTE algorithm, which creates synthetic data, however, they focus on local information rather than the overall class distribution. In this work, we explore a novel approach to handle the data imbalance issue based on Generative Adversarial Networks (GANs) which use the overall data distribution. GANs are utilized to generate synthetic data that closely resembles the real one, thus this generated data can be employed to enhance the ML models' performance by eradicating the class imbalance problem for biological sequence analysis. We perform 3 distinct classification tasks by using 3 different sequence datasets (Influenza A Virus, PALMdb, VDjDB) and our results illustrate that GANs can improve the overall classification performance.

Sarwan Ali, Babatunde Bello, Prakash Chourasia et al.

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.

Sarwan Ali, Prakash Chourasia, Zahra Tayebi et al.

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.

Mansoor Ahmed, Usama Sardar, Sarwan Ali et al.

The determination of biological brain age is a crucial biomarker in the assessment of neurological disorders and understanding of the morphological changes that occur during aging. Various machine learning models have been proposed for estimating brain age through Magnetic Resonance Imaging (MRI) of healthy controls. However, developing a robust brain age estimation (BAE) framework has been challenging due to the selection of appropriate MRI-derived features and the high cost of MRI acquisition. In this study, we present a novel BAE framework using the Open Big Healthy Brain (OpenBHB) dataset, which is a new multi-site and publicly available benchmark dataset that includes region-wise feature metrics derived from T1-weighted (T1-w) brain MRI scans of 3965 healthy controls aged between 6 to 86 years. Our approach integrates three different MRI-derived region-wise features and different regression models, resulting in a highly accurate brain age estimation with a Mean Absolute Error (MAE) of 3.25 years, demonstrating the framework's robustness. We also analyze our model's regression-based performance on gender-wise (male and female) healthy test groups. The proposed BAE framework provides a new approach for estimating brain age, which has important implications for the understanding of neurological disorders and age-related brain changes.

Taslim Murad, Prakash Chourasia, Sarwan Ali et al.

Cancer is a complex disease characterized by uncontrolled cell growth. T cell receptors (TCRs), crucial proteins in the immune system, play a key role in recognizing antigens, including those associated with cancer. Recent advancements in sequencing technologies have facilitated comprehensive profiling of TCR repertoires, uncovering TCRs with potent anti-cancer activity and enabling TCR-based immunotherapies. However, analyzing these intricate biomolecules necessitates efficient representations that capture their structural and functional information. T-cell protein sequences pose unique challenges due to their relatively smaller lengths compared to other biomolecules. An image-based representation approach becomes a preferred choice for efficient embeddings, allowing for the preservation of essential details and enabling comprehensive analysis of T-cell protein sequences. In this paper, we propose to generate images from the protein sequences using the idea of Chaos Game Representation (CGR) using the Kaleidoscopic images approach. This Deep Learning Assisted Analysis of Protein Sequences Using Chaos Enhanced Kaleidoscopic Images (called DANCE) provides a unique way to visualize protein sequences by recursively applying chaos game rules around a central seed point. we perform the classification of the T cell receptors (TCRs) protein sequences in terms of their respective target cancer cells, as TCRs are known for their immune response against cancer disease. The TCR sequences are converted into images using the DANCE method. We employ deep-learning vision models to perform the classification to obtain insights into the relationship between the visual patterns observed in the generated kaleidoscopic images and the underlying protein properties. By combining CGR-based image generation with deep learning classification, this study opens novel possibilities in the protein analysis domain.

Zahra Tayebi, Sarwan Ali, Prakash Chourasia et al.

Cancer is a complex disease characterized by uncontrolled cell growth and proliferation. T cell receptors (TCRs) are essential proteins for the adaptive immune system, and their specific recognition of antigens plays a crucial role in the immune response against diseases, including cancer. The diversity and specificity of TCRs make them ideal for targeting cancer cells, and recent advancements in sequencing technologies have enabled the comprehensive profiling of TCR repertoires. This has led to the discovery of TCRs with potent anti-cancer activity and the development of TCR-based immunotherapies. In this study, we investigate the use of sparse coding for the multi-class classification of TCR protein sequences with cancer categories as target labels. Sparse coding is a popular technique in machine learning that enables the representation of data with a set of informative features and can capture complex relationships between amino acids and identify subtle patterns in the sequence that might be missed by low-dimensional methods. We first compute the k-mers from the TCR sequences and then apply sparse coding to capture the essential features of the data. To improve the predictive performance of the final embeddings, we integrate domain knowledge regarding different types of cancer properties. We then train different machine learning (linear and non-linear) classifiers on the embeddings of TCR sequences for the purpose of supervised analysis. Our proposed embedding method on a benchmark dataset of TCR sequences significantly outperforms the baselines in terms of predictive performance, achieving an accuracy of 99.8\%. Our study highlights the potential of sparse coding for the analysis of TCR protein sequences in cancer research and other related fields.

Sarwan Ali, Usama Sardar, Murray Patterson et al.

Representation learning is an important step in the machine learning pipeline. Given the current biological sequencing data volume, learning an explicit representation is prohibitive due to the dimensionality of the resulting feature vectors. Kernel-based methods, e.g., SVM, are a proven efficient and useful alternative for several machine learning (ML) tasks such as sequence classification. Three challenges with kernel methods are (i) the computation time, (ii) the memory usage (storing an $n\times n$ matrix), and (iii) the usage of kernel matrices limited to kernel-based ML methods (difficult to generalize on non-kernel classifiers). While (i) can be solved using approximate methods, challenge (ii) remains for typical kernel methods. Similarly, although non-kernel-based ML methods can be applied to kernel matrices by extracting principal components (kernel PCA), it may result in information loss, while being computationally expensive. In this paper, we propose a general-purpose representation learning approach that embodies kernel methods' qualities while avoiding computation, memory, and generalizability challenges. This involves computing a low-dimensional embedding of each sequence, using random projections of its $k$-mer frequency vectors, significantly reducing the computation needed to compute the dot product and the memory needed to store the resulting representation. Our proposed fast and alignment-free embedding method can be used as input to any distance (e.g., $k$ nearest neighbors) and non-distance (e.g., decision tree) based ML method for classification and clustering tasks. Using different forms of biological sequences as input, we perform a variety of real-world classification tasks, such as SARS-CoV-2 lineage and gene family classification, outperforming several state-of-the-art embedding and kernel methods in predictive performance.

Sarwan Ali, Taslim Murad, Murray Patterson

Coronaviruses are membrane-enveloped, non-segmented positive-strand RNA viruses belonging to the Coronaviridae family. Various animal species, mainly mammalian and avian, are severely infected by various coronaviruses, causing serious concerns like the recent pandemic (COVID-19). Therefore, building a deeper understanding of these viruses is essential to devise prevention and mitigation mechanisms. In the Coronavirus genome, an essential structural region is the spike region, and it's responsible for attaching the virus to the host cell membrane. Therefore, the usage of only the spike protein, instead of the full genome, provides most of the essential information for performing analyses such as host classification. In this paper, we propose a novel method for predicting the host specificity of coronaviruses by analyzing spike protein sequences from different viral subgenera and species. Our method involves using the Poisson correction distance to generate a distance matrix, followed by using a radial basis function (RBF) kernel and kernel principal component analysis (PCA) to generate a low-dimensional embedding. Finally, we apply classification algorithms to the low-dimensional embedding to generate the resulting predictions of the host specificity of coronaviruses. We provide theoretical proofs for the non-negativity, symmetry, and triangle inequality properties of the Poisson correction distance metric, which are important properties in a machine-learning setting. By encoding the spike protein structure and sequences using this comprehensive approach, we aim to uncover hidden patterns in the biological sequences to make accurate predictions about host specificity. Finally, our classification results illustrate that our method can achieve higher predictive accuracy and improve performance over existing baselines.

Sarwan Ali, Prakash Chourasia, Murray Patterson

Anderson acceleration (AA) is a well-known method for accelerating the convergence of iterative algorithms, with applications in various fields including deep learning and optimization. Despite its popularity in these areas, the effectiveness of AA in classical machine learning classifiers has not been thoroughly studied. Tabular data, in particular, presents a unique challenge for deep learning models, and classical machine learning models are known to perform better in these scenarios. However, the convergence analysis of these models has received limited attention. To address this gap in research, we implement a support vector machine (SVM) classifier variant that incorporates AA to speed up convergence. We evaluate the performance of our SVM with and without Anderson acceleration on several datasets from the biology domain and demonstrate that the use of AA significantly improves convergence and reduces the training loss as the number of iterations increases. Our findings provide a promising perspective on the potential of Anderson acceleration in the training of simple machine learning classifiers and underscore the importance of further research in this area. By showing the effectiveness of AA in this setting, we aim to inspire more studies that explore the applications of AA in classical machine learning.

Mansoor Ahmed, Spencer VonBank, Nadeem Taj et al.

Computational antibody CDR design methods condition on antigen structure to generate binding loops, yet existing architectures conflate two fundamentally distinct sub-problems: identifying which CDR positions will contact the antigen, and selecting amino acids at those positions. This conflation forces models to learn contact reasoning implicitly through uniform message passing, diluting antigen signal across all positions equally. We introduce ConTact, a contact-then-act architecture that explicitly decomposes CDR design into three cascaded stages: learning surface complementarity fingerprints, predicting CDR-antigen contacts, and injecting contact-gated antigen features into the sequence head. A distance-biased cross-attention module encodes geometric priors favoring spatial neighbors, while a contact-weighted cross-entropy loss concentrates gradient signal on binding-critical positions. On CHIMERA-Bench dataset, ConTact achieves the best structural quality (7% RMSD improvement over the next-best baseline), best epitope awareness (10% F1 score over GNN baselines), and competitive sequence recovery (AAR 0.38) among several CDR-H3 design baselines.

Mansoor Ahmed, Sujin Lee, Umar Khayaz et al.

Equivariant graph neural network (GNN) methods for antibody complementarity-determining region (CDR) design achieve the highest sequence recovery but suffer from severe vocabulary collapse. The current best GNN methods over-predict very few amino acids, such as tyrosine and glycine, while ignoring functionally important residues. We trace this failure to GNN encoders learning amino acid distributions de novo from limited structural data, discarding substitution patterns encoded in evolutionary databases. To resolve this, we propose EvoStruct, which bridges a frozen protein language model (PLM) with 3D structural context from an E(3)-equivariant GNN via a cross-attention adapter. Unlike prior PLM-structure adapters for general protein design, EvoStruct targets the vocabulary collapse problem specific to CDR design through progressive PLM unfreezing and R-Drop consistency regularization. On the CHIMERA-Bench dataset, EvoStruct achieves the highest amino acid recovery and lowest perplexity among several antibody design methods, improving sequence recovery by 16% and reducing perplexity by 43% relative to the best GNN baselines, while recovering 2.3x greater amino acid diversity and the highest binding-pair correlation with ground truth.

Sarwan Ali, Prakash Chourasia, Bipin Koirala et al.

Molecular sequence analysis is crucial for comprehending several biological processes, including protein-protein interactions, functional annotation, and disease classification. The large number of sequences and the inherently complicated nature of protein structures make it challenging to analyze such data. Finding patterns and enhancing subsequent research requires the use of dimensionality reduction and feature selection approaches. Recently, a method called Correlated Clustering and Projection (CCP) has been proposed as an effective method for biological sequencing data. The CCP technique is still costly to compute even though it is effective for sequence visualization. Furthermore, its utility for classifying molecular sequences is still uncertain. To solve these two problems, we present a Nearest Neighbor Correlated Clustering and Projection (CCP-NN)-based technique for efficiently preprocessing molecular sequence data. To group related molecular sequences and produce representative supersequences, CCP makes use of sequence-to-sequence correlations. As opposed to conventional methods, CCP doesn't rely on matrix diagonalization, therefore it can be applied to a range of machine-learning problems. We estimate the density map and compute the correlation using a nearest-neighbor search technique. We performed molecular sequence classification using CCP and CCP-NN representations to assess the efficacy of our proposed approach. Our findings show that CCP-NN considerably improves classification task accuracy as well as significantly outperforms CCP in terms of computational runtime.

Avais Jan, Prakash Chourasia, Sarwan Ali et al.

Dimensionality reduction techniques are essential for visualizing and analyzing high-dimensional biological sequencing data. t-distributed Stochastic Neighbor Embedding (t-SNE) is widely used for this purpose, traditionally employing the Gaussian kernel to compute pairwise similarities. However, the Gaussian kernel's lack of data-dependence and computational overhead limit its scalability and effectiveness for categorical biological sequences. Recent work proposed the isolation kernel as an alternative, yet it may not optimally capture sequence similarities. In this study, we comprehensively evaluate nine different kernel functions for t-SNE applied to molecular sequences, using three embedding methods: One-Hot Encoding, Spike2Vec, and minimizers. Through both subjective visualization and objective metrics (including neighborhood preservation scores), we demonstrate that the cosine similarity kernel in general outperforms other kernels, including Gaussian and isolation kernels, achieving superior runtime efficiency and better preservation of pairwise distances in low-dimensional space. We further validate our findings through extensive classification and clustering experiments across six diverse biological datasets (Spike7k, Host, ShortRead, Rabies, Genome, and Breast Cancer), employing multiple machine learning algorithms and evaluation metrics. Our results show that kernel selection significantly impacts not only visualization quality but also downstream analytical tasks, with the cosine similarity kernel providing the most robust performance across different data types and embedding strategies, making it particularly suitable for large-scale biological sequence analysis.

Sarwan Ali, Tamkanat E Ali, Prakash Chourasia et al.

In the field of biological research, it is essential to comprehend the characteristics and functions of molecular sequences. The classification of molecular sequences has seen widespread use of neural network-based techniques. Despite their astounding accuracy, these models often require a substantial number of parameters and more data collection. In this work, we present a novel approach based on the compression-based Model, motivated from \cite{jiang2023low}, which combines the simplicity of basic compression algorithms like Gzip and Bz2, with Normalized Compression Distance (NCD) algorithm to achieve better performance on classification tasks without relying on handcrafted features or pre-trained models. Firstly, we compress the molecular sequence using well-known compression algorithms, such as Gzip and Bz2. By leveraging the latent structure encoded in compressed files, we compute the Normalized Compression Distance between each pair of molecular sequences, which is derived from the Kolmogorov complexity. This gives us a distance matrix, which is the input for generating a kernel matrix using a Gaussian kernel. Next, we employ kernel Principal Component Analysis (PCA) to get the vector representations for the corresponding molecular sequence, capturing important structural and functional information. The resulting vector representations provide an efficient yet effective solution for molecular sequence analysis and can be used in ML-based downstream tasks. The proposed approach eliminates the need for computationally intensive Deep Neural Networks (DNNs), with their large parameter counts and data requirements. Instead, it leverages a lightweight and universally accessible compression-based model.

Taslim Murad, Sarwan Ali, Murray Patterson

The analysis of sequences (e.g., protein, DNA, and SMILES string) is essential for disease diagnosis, biomaterial engineering, genetic engineering, and drug discovery domains. Conventional analytical methods focus on transforming sequences into numerical representations for applying machine learning/deep learning-based sequence characterization. However, their efficacy is constrained by the intrinsic nature of deep learning (DL) models, which tend to exhibit suboptimal performance when applied to tabular data. An alternative group of methodologies endeavors to convert biological sequences into image forms by applying the concept of Chaos Game Representation (CGR). However, a noteworthy drawback of these methods lies in their tendency to map individual elements of the sequence onto a relatively small subset of designated pixels within the generated image. The resulting sparse image representation may not adequately encapsulate the comprehensive sequence information, potentially resulting in suboptimal predictions. In this study, we introduce a novel approach to transform sequences into images using the Bézier curve concept for element mapping. Mapping the elements onto a curve enhances the sequence information representation in the respective images, hence yielding better DL-based classification performance. We employed different sequence datasets to validate our system by using different classification tasks, and the results illustrate that our Bézier curve method is able to achieve good performance for all the tasks.

Sarwan Ali, Prakash Chourasia, Murray Patterson

This study introduces a novel approach, combining substruct counting, $k$-mers, and Daylight-like fingerprints, to expand the representation of chemical structures in SMILES strings. The integrated method generates comprehensive molecular embeddings that enhance discriminative power and information content. Experimental evaluations demonstrate its superiority over traditional Morgan fingerprinting, MACCS, and Daylight fingerprint alone, improving chemoinformatics tasks such as drug classification. The proposed method offers a more informative representation of chemical structures, advancing molecular similarity analysis and facilitating applications in molecular design and drug discovery. It presents a promising avenue for molecular structure analysis and design, with significant potential for practical implementation.

Sarwan Ali, Taslim Murad, Prakash Chourasia et al.

Understanding the structural and functional characteristics of proteins are crucial for developing preventative and curative strategies that impact fields from drug discovery to policy development. An important and popular technique for examining how amino acids make up these characteristics of the protein sequences with position-specific scoring (PSS). While the string kernel is crucial in natural language processing (NLP), it is unclear if string kernels can extract biologically meaningful information from protein sequences, despite the fact that they have been shown to be effective in the general sequence analysis tasks. In this work, we propose a weighted PSS kernel matrix (or W-PSSKM), that combines a PSS representation of protein sequences, which encodes the frequency information of each amino acid in a sequence, with the notion of the string kernel. This results in a novel kernel function that outperforms many other approaches for protein sequence classification. We perform extensive experimentation to evaluate the proposed method. Our findings demonstrate that the W-PSSKM significantly outperforms existing baselines and state-of-the-art methods and achieves up to 45.1\% improvement in classification accuracy.

Sarwan Ali, Haris Mansoor, Murray Patterson

Genomic sequence analysis plays a crucial role in various scientific and medical domains. Traditional machine-learning approaches often struggle to capture the complex relationships and hierarchical structures of sequence data when working in high-dimensional Euclidean spaces. This limitation hinders accurate sequence classification and similarity measurement. To address these challenges, this research proposes a method to transform the feature representation of biological sequences into the hyperboloid space. By applying a transformation, the sequences are mapped onto the hyperboloid, preserving their inherent structural information. Once the sequences are represented in the hyperboloid space, a kernel matrix is computed based on the hyperboloid features. The kernel matrix captures the pairwise similarities between sequences, enabling more effective analysis of biological sequence relationships. This approach leverages the inner product of the hyperboloid feature vectors to measure the similarity between pairs of sequences. The experimental evaluation of the proposed approach demonstrates its efficacy in capturing important sequence correlations and improving classification accuracy.

Qasim Zia, Avais Jan, Zafar Iqbal et al.

Cardiac arrest is one of the biggest global health problems, and early identification and management are key to enhancing the patient's prognosis. In this paper, we propose a novel framework that combines an EfficientNet-based deep learning model with a digital twin system to improve the early detection and analysis of cardiac arrest. We use compound scaling and EfficientNet to learn the features of cardiovascular images. In parallel, the digital twin creates a realistic and individualized cardiovascular system model of the patient based on data received from the Internet of Things (IoT) devices attached to the patient, which can help in the constant assessment of the patient and the impact of possible treatment plans. As shown by our experiments, the proposed system is highly accurate in its prediction abilities and, at the same time, efficient. Combining highly advanced techniques such as deep learning and digital twin (DT) technology presents the possibility of using an active and individual approach to predicting cardiac disease.

Avais Jan, Qasim Zia, Murray Patterson

The application of Digital Twin (DT) technology and Federated Learning (FL) has great potential to change the field of biomedical image analysis, particularly for Computed Tomography (CT) scans. This paper presents Federated Transfer Learning (FTL) as a new Digital Twin-based CT scan analysis paradigm. FTL uses pre-trained models and knowledge transfer between peer nodes to solve problems such as data privacy, limited computing resources, and data heterogeneity. The proposed framework allows real-time collaboration between cloud servers and Digital Twin-enabled CT scanners while protecting patient identity. We apply the FTL method to a heterogeneous CT scan dataset and assess model performance using convergence time, model accuracy, precision, recall, F1 score, and confusion matrix. It has been shown to perform better than conventional FL and Clustered Federated Learning (CFL) methods with better precision, accuracy, recall, and F1-score. The technique is beneficial in settings where the data is not independently and identically distributed (non-IID), and it offers reliable, efficient, and secure solutions for medical diagnosis. These findings highlight the possibility of using FTL to improve decision-making in digital twin-based CT scan analysis, secure and efficient medical image analysis, promote privacy, and open new possibilities for applying precision medicine and smart healthcare systems.

Sarwan Ali, Tamkanat E Ali, Imdad Ullah Khan et al.

In the realm of data analysis and bioinformatics, representing time series data in a manner akin to biological sequences offers a novel approach to leverage sequence analysis techniques. Transforming time series signals into molecular sequence-type representations allows us to enhance pattern recognition by applying sophisticated sequence analysis techniques (e.g. $k$-mers based representation) developed in bioinformatics, uncovering hidden patterns and relationships in complex, non-linear time series data. This paper proposes a method to transform time series signals into biological/molecular sequence-type representations using a unique alphabetic mapping technique. By generating 26 ranges corresponding to the 26 letters of the English alphabet, each value within the time series is mapped to a specific character based on its range. This conversion facilitates the application of sequence analysis algorithms, typically used in bioinformatics, to analyze time series data. We demonstrate the effectiveness of this approach by converting real-world time series signals into character sequences and performing sequence classification. The resulting sequences can be utilized for various sequence-based analysis techniques, offering a new perspective on time series data representation and analysis.

Sarwan Ali, Tamkanat E Ali, Imdad Ullah Khan et al.

Accurate molecular sequence analysis is a key task in the field of bioinformatics. To apply molecular sequence classification algorithms, we first need to generate the appropriate representations of the sequences. Traditional numeric sequence representation techniques are mostly based on sequence alignment that faces limitations in the form of lack of accuracy. Although several alignment-free techniques have also been introduced, their tabular data form results in low performance when used with Deep Learning (DL) models compared to the competitive performance observed in the case of image-based data. To find a solution to this problem and to make Deep Learning (DL) models function to their maximum potential while capturing the important spatial information in the sequence data, we propose a universal Hibert curve-based Chaos Game Representation (CGR) method. This method is a transformative function that involves a novel Alphabetic index mapping technique used in constructing Hilbert curve-based image representation from molecular sequences. Our method can be globally applied to any type of molecular sequence data. The Hilbert curve-based image representations can be used as input to sophisticated vision DL models for sequence classification. The proposed method shows promising results as it outperforms current state-of-the-art methods by achieving a high accuracy of $94.5$\% and an F1 score of $93.9\%$ when tested with the CNN model on the lung cancer dataset. This approach opens up a new horizon for exploring molecular sequence analysis using image classification methods.

Sarwan Ali, Haris Mansoor, Prakash Chourasia et al.

In molecular structure data, SMILES (Simplified Molecular Input Line Entry System) strings are used to analyze molecular structure design. Numerical feature representation of SMILES strings is a challenging task. This work proposes a kernel-based approach for encoding and analyzing molecular structures from SMILES strings. The proposed approach involves computing a kernel matrix using the Sinkhorn-Knopp algorithm while using kernel principal component analysis (PCA) for dimensionality reduction. The resulting low-dimensional embeddings are then used for classification and regression analysis. The kernel matrix is computed by converting the SMILES strings into molecular structures using the Morgan Fingerprint, which computes a fingerprint for each molecule. The distance matrix is computed using the pairwise kernels function. The Sinkhorn-Knopp algorithm is used to compute the final kernel matrix that satisfies the constraints of a probability distribution. This is achieved by iteratively adjusting the kernel matrix until the marginal distributions of the rows and columns match the desired marginal distributions. We provided a comprehensive empirical analysis of the proposed kernel method to evaluate its goodness with greater depth. The suggested method is assessed for drug subcategory prediction (classification task) and solubility AlogPS ``Aqueous solubility and Octanol/Water partition coefficient" (regression task) using the benchmark SMILES string dataset. The outcomes show the proposed method outperforms several baseline methods in terms of supervised analysis and has potential uses in molecular design and drug discovery. Overall, the suggested method is a promising avenue for kernel methods-based molecular structure analysis and design.

Taslim Murad, Prakash Chourasia, Sarwan Ali et al.

The availability of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus data post-COVID has reached exponentially to an enormous magnitude, opening research doors to analyze its behavior. Various studies are conducted by researchers to gain a deeper understanding of the virus, like genomic surveillance, etc, so that efficient prevention mechanisms can be developed. However, the unstable nature of the virus (rapid mutations, multiple hosts, etc) creates challenges in designing analytical systems for it. Therefore, we propose a neural network-based (NN) mechanism to perform an efficient analysis of the SARS-CoV-2 data, as NN portrays generalized behavior upon training. Moreover, rather than using the full-length genome of the virus, we apply our method to its spike region, as this region is known to have predominant mutations and is used to attach to the host cell membrane. In this paper, we introduce a pipeline that first converts the spike protein sequences into a fixed-length numerical representation and then uses Neuromorphic Spiking Neural Network to classify those sequences. We compare the performance of our method with various baselines using real-world SARS-CoV-2 spike sequence data and show that our method is able to achieve higher predictive accuracy compared to the recent baselines.

Ahmed Luqman, Khuzemah Qazi, Murray Patterson et al.

Despite the success of CNN models on a variety of Image classification and segmentation tasks, their extensive computational and storage demands pose considerable challenges for real-world deployment on resource-constrained devices. Quantization is one technique that aims to alleviate these large storage requirements and speed up the inference process by reducing the precision of model parameters to lower-bit representations. In this paper, we introduce a novel post-training quantization method for model weights. Our method finds optimal clipping thresholds and scaling factors along with mathematical guarantees that our method minimizes quantization noise. Empirical results on real-world datasets demonstrate that our quantization scheme significantly reduces model size and computational requirements while preserving model accuracy.

Prakash Chourasia, Heramb Lonkar, Sarwan Ali et al.

Advancements in genomics technology lead to a rising volume of viral (e.g., SARS-CoV-2) sequence data, resulting in increased usage of machine learning (ML) in bioinformatics. Traditional ML techniques require centralized data collection and processing, posing challenges in realistic healthcare scenarios. Additionally, privacy, ownership, and stringent regulation issues exist when pooling medical data into centralized storage to train a powerful deep learning (DL) model. The Federated learning (FL) approach overcomes such issues by setting up a central aggregator server and a shared global model. It also facilitates data privacy by extracting knowledge while keeping the actual data private. This work proposes a cutting-edge Privacy enhancement through Iterative Collaboration (EPIC) architecture. The network is divided and distributed between local and centralized servers. We demonstrate the EPIC approach to resolve a supervised classification problem to estimate SARS-CoV-2 genomic sequence data lineage without explicitly transferring raw sequence data. We aim to create a universal decentralized optimization framework that allows various data holders to work together and converge to a single predictive model. The findings demonstrate that privacy-preserving strategies can be successfully used with aggregation approaches without materially altering the degree of learning convergence. Finally, we highlight a few potential issues and prospects for study in FL-based approaches to healthcare applications.

Sarwan Ali, Prakash Chourasia, Haris Mansoor et al.

The t-Distributed Stochastic Neighbor Embedding (t-SNE) has emerged as a popular dimensionality reduction technique for visualizing high-dimensional data. It computes pairwise similarities between data points by default using an RBF kernel and random initialization (in low-dimensional space), which successfully captures the overall structure but may struggle to preserve the local structure efficiently. This research proposes a novel approach called the Modified Isolation Kernel (MIK) as an alternative to the Gaussian kernel, which is built upon the concept of the Isolation Kernel. MIK uses adaptive density estimation to capture local structures more accurately and integrates robustness measures. It also assigns higher similarity values to nearby points and lower values to distant points. Comparative research using the normal Gaussian kernel, the isolation kernel, and several initialization techniques, including random, PCA, and random walk initializations, are used to assess the proposed approach (MIK). Additionally, we compare the computational efficiency of all $3$ kernels with $3$ different initialization methods. Our experimental results demonstrate several advantages of the proposed kernel (MIK) and initialization method selection. It exhibits improved preservation of the local and global structure and enables better visualization of clusters and subclusters in the embedded space. These findings contribute to advancing dimensionality reduction techniques and provide researchers and practitioners with an effective tool for data exploration, visualization, and analysis in various domains.

Sarwan Ali, Babatunde Bello, Prakash Chourasia et al.

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.

Zahra Tayebi, Sarwan Ali, Murray Patterson

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. One one had, this will help biologists, policy makers 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. 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). Hence, in this paper, we propose an approach to cluster spike protein sequences in order to study the behavior of different known variants that are increasing at very high rate throughout the world. We use a k-mers based approach to first generate a fixed-length feature vector representation for the spike sequences. We then show that with the appropriate feature selection, we can efficiently and effectively cluster the spike sequences based on the different variants. 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.

Sarwan Ali, Yijing Zhou, Murray Patterson

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 important 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 for 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 on 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 policy makers to focus on only certain attributes for the purposes of studying this disease rather than focusing on multiple random factors that may not be very informative to patient outcomes.

Sarwan Ali, Babatunde Bello, Zahra Tayebi et al.

With the rapid spread of COVID-19 worldwide, viral genomic data is available in the order of millions of sequences on public databases such as GISAID. This Big Data creates a unique opportunity for analysis towards 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 paper, 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.

Sarwan Ali, Murray Patterson

With the rapid global spread of COVID-19, more and more data related to this virus is becoming available, including genomic sequence data. The total number of genomic sequences that are publicly available on platforms such as GISAID is currently several million, and is increasing with every day. The availability of such \emph{Big Data} creates a new opportunity for researchers to study this virus in detail. This is particularly important with all of the dynamics of the COVID-19 variants which emerge and circulate. This rich data source will give us insights on the best ways to perform genomic surveillance for this and future pandemic threats, with the ultimate goal of mitigating or eliminating such threats. Analyzing and processing the several million genomic sequences is a challenging task. Although traditional methods for sequence classification are proven to be effective, they are not designed to deal with these specific types of genomic sequences. Moreover, most of the existing methods also face the issue of scalability. Previous studies which were tailored to coronavirus genomic data proposed to use spike sequences (corresponding to a subsequence of the genome), rather than using the complete genomic sequence, to perform different machine learning (ML) tasks such as classification and clustering. However, those methods suffer from scalability issues. In this paper, we propose an approach called Spike2Vec, an efficient and scalable feature vector representation for each spike sequence that can be used for downstream ML tasks. Through experiments, we show that Spike2Vec is not only scalable on several million spike sequences, but also outperforms the baseline models in terms of prediction accuracy, F1 score, etc.

Sarwan Ali, Tamkanat-E-Ali, Muhammad Asad Khan et al.

SARS-CoV-2, like any other virus, continues to mutate as it spreads, according to an evolutionary process. Unlike any other virus, the number of currently available sequences of SARS-CoV-2 in public databases such as GISAID is already several million. This amount of data has the potential to uncover the evolutionary dynamics of a virus like never before. However, a million is already several orders of magnitude beyond what can be processed by the traditional methods designed to reconstruct a virus's evolutionary history, such as those that build a phylogenetic tree. Hence, new and scalable methods will need to be devised in order to make use of the ever increasing number of viral sequences being collected. Since identifying variants is an important part of understanding the evolution of a virus, in this paper, we propose an approach based on clustering sequences to identify the current major SARS-CoV-2 variants. Using a $k$-mer based feature vector generation and efficient feature selection methods, our approach is effective in identifying variants, as well as being efficient and scalable to millions of sequences. Such a clustering method allows us to show the relative proportion of each variant over time, giving the rate of spread of each variant in different locations -- something which is important for vaccine development and distribution. We also compute the importance of each amino acid position of the spike protein in identifying a given variant in terms of information gain. Positions of high variant-specific importance tend to agree with those reported by the USA's Centers for Disease Control and Prevention (CDC), further demonstrating our approach.

Sarwan Ali, Bikram Sahoo, Naimat Ullah et al.

With the rapid spread of the novel coronavirus (COVID-19) across the globe and its continuous mutation, it is of pivotal importance to design a system to identify different known (and unknown) variants of SARS-CoV-2. Identifying particular variants helps to understand and model their spread patterns, design effective mitigation strategies, and prevent future outbreaks. It also plays a crucial role in studying the efficacy of known vaccines against each variant and modeling the likelihood of breakthrough infections. It is well known that the spike protein contains most of the information/variation pertaining to coronavirus variants. In this paper, we use spike sequences to classify different variants of the coronavirus in humans. We show that preserving the order of the amino acids helps the underlying classifiers to achieve better performance. We also show that we can train our model to outperform the baseline algorithms using only a small number of training samples ($1\%$ of the data). Finally, we show the importance of the different amino acids which play a key role in identifying variants and how they coincide with those reported by the USA's Centers for Disease Control and Prevention (CDC).