Converting Time Series Data to Numeric Representations Using Alphabetic Mapping and k-mer strategy

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.

Hilbert Curve Based Molecular Sequence Analysis

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.

Computing Gram Matrix for SMILES Strings using RDKFingerprint and Sinkhorn-Knopp Algorithm

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.

EPIC: Enhancing Privacy through Iterative Collaboration

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.

DWFL: Enhancing Federated Learning through Dynamic Weighted Averaging

Federated Learning (FL) is a distributed learning technique that maintains data privacy by providing a decentralized training method for machine learning models using distributed big data. This promising Federated Learning approach has also gained popularity in bioinformatics, where the privacy of biomedical data holds immense importance, especially when patient data is involved. Despite the successful implementation of Federated learning in biological sequence analysis, rigorous consideration is still required to improve accuracy in a way that data privacy should not be compromised. Additionally, the optimal integration of federated learning, especially in protein sequence analysis, has not been fully explored. We propose a deep feed-forward neural network-based enhanced federated learning method for protein sequence classification to overcome these challenges. Our method introduces novel enhancements to improve classification accuracy. We introduce dynamic weighted federated learning (DWFL) which is a federated learning-based approach, where local model weights are adjusted using weighted averaging based on their performance metrics. By assigning higher weights to well-performing models, we aim to create a more potent initial global model for the federated learning process, leading to improved accuracy. We conduct experiments using real-world protein sequence datasets to assess the effectiveness of DWFL. The results obtained using our proposed approach demonstrate significant improvements in model accuracy, making federated learning a preferred, more robust, and privacy-preserving approach for collaborative machine-learning tasks.

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.