Expanding Chemical Representation with k-mers and Fragment-based Fingerprints for Molecular Fingerprinting

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.

A Universal Non-Parametric Approach For Improved Molecular Sequence Analysis

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.

T Cell Receptor Protein Sequences and Sparse Coding: A Novel Approach to Cancer Classification

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.

Virus2Vec: Viral Sequence Classification Using Machine Learning

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.

ViralVectors: Compact and Scalable Alignment-free Virome Feature Generation

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.

Efficient Classification of SARS-CoV-2 Spike Sequences Using Federated Learning

This paper presents a federated learning (FL) approach to train an AI model for SARS-Cov-2 coronavirus variant identification. We analyze the SARS-CoV-2 spike sequences in a distributed way, without data sharing, to detect different variants of the rapidly mutating coronavirus. A vast amount of sequencing data of SARS-CoV-2 is available due to various genomic monitoring initiatives by several nations. However, privacy concerns involving patient health information and national public health conditions could hinder openly sharing this data. In this work, we propose a lightweight FL paradigm to cooperatively analyze the spike protein sequences of SARS-CoV-2 privately, using the locally stored data to train a prediction model from remote nodes. 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. We compare the performance of our approach on spike sequence data with the recently proposed state-of-the-art methods for classification from spike sequences. Using the proposed approach, we achieve an overall accuracy of $93\%$ on the coronavirus variant identification task. To the best of our knowledge, this is the first work in the federated learning paradigm for biological sequence analysis. Since the proposed model is distributed in nature, it could scale on ``Big Data'' easily. We plan to use this proof-of-concept to implement a privacy-preserving pandemic response strategy.

Anderson Acceleration For Bioinformatics-Based Machine Learning

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.

Informative Initialization and Kernel Selection Improves t-SNE for Biological Sequences

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.

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 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.

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

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.