MIK: Modified Isolation Kernel for Biological Sequence Visualization, Classification, and Clustering

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.

Position Specific Scoring Is All You Need? Revisiting Protein Sequence Classification Tasks

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.

DANCE: Deep Learning-Assisted Analysis of Protein Sequences Using Chaos Enhanced Kaleidoscopic Images

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.

Nearest Neighbor CCP-Based Molecular Sequence Analysis

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.

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.

Sequence-Based Nanobody-Antigen Binding Prediction

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.

Robust Brain Age Estimation via Regression Models and MRI-derived Features

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.

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.