Biological Datasets Research Articles

Advancements in Multiple Myeloma Research: High-Throughput Sequencing Technologies, Omics, and the Role of Artificial Intelligence

Multiple myeloma is a complex and challenging type of blood cancer that affects plasma cells in the bone marrow. In recent years, the development of advanced research techniques, such as omics approaches—which involve studying large sets of biological data like genes and proteins—and high-throughput sequencing technologies, has allowed researchers to analyze vast amounts of genetic information rapidly and gain new insights into the disease. Additionally, the advent of artificial intelligence tools has accelerated data analysis, enabling more accurate predictions and improved treatment strategies. This review aims to highlight recent research advances in multiple myeloma made possible by these novel techniques and to provide guidance for researchers seeking effective approaches in this field.

Personalized cancer vaccine design using AI-powered technologies

Immunotherapy has ushered in a new era of cancer treatment, yet cancer remains a leading cause of global mortality. Among various therapeutic strategies, cancer vaccines have shown promise by activating the immune system to specifically target cancer cells. While current cancer vaccines are primarily prophylactic, advancements in targeting tumor-associated antigens (TAAs) and neoantigens have paved the way for therapeutic vaccines. The integration of artificial intelligence (AI) into cancer vaccine development is revolutionizing the field by enhancing various aspect of design and delivery. This review explores how AI facilitates precise epitope design, optimizes mRNA and DNA vaccine instructions, and enables personalized vaccine strategies by predicting patient responses. By utilizing AI technologies, researchers can navigate complex biological datasets and uncover novel therapeutic targets, thereby improving the precision and efficacy of cancer vaccines. Despite the promise of AI-powered cancer vaccines, significant challenges remain, such as tumor heterogeneity and genetic variability, which can limit the effectiveness of neoantigen prediction. Moreover, ethical and regulatory concerns surrounding data privacy and algorithmic bias must be addressed to ensure responsible AI deployment. The future of cancer vaccine development lies in the seamless integration of AI to create personalized immunotherapies that offer targeted and effective cancer treatments. This review underscores the importance of interdisciplinary collaboration and innovation in overcoming these challenges and advancing cancer vaccine development.

Introducing CHiDO-A No Code Genomic Prediction software implementation for the characterization and integration of driven omics.

Climate change represents a significant challenge to global food security by altering environmental conditions critical to crop growth. Plant breeders can play a key role in mitigating these challenges by developing more resilient crop varieties; however, these efforts require significant investments in resources and time. In response, it is imperative to use current technologies that assimilate large biological and environmental datasets into predictive models to accelerate the research, development, and release of new improved varieties that can be more resilient to the increasingly variable climatic conditions. Leveraging large and diverse datasets can improve the characterization of phenotypic responses due to environmental stimuli and genomic pulses. A better characterization of these signals holds the potential to enhance our ability to predict trait performance under changes in weather and/or soil conditions with high precision. This paper introduces characterization and integration of driven omics (CHiDO), an easy-to-use, no-code platform designed to integrate diverse omics datasets and effectively model their interactions. With its flexibility to integrate and process datasets, CHiDO's intuitive interface allows users to explore historical data, formulate hypotheses, and optimize data collection strategies for future scenarios. The platform's mission emphasizes global accessibility, democratizing statistical solutions for situations where professional ability in data processing and data analysis is not available.

Gentrius: Generating Trees Compatible With a Set of Unrooted Subtrees and its Application to Phylogenetic Terraces.

For a set of binary unrooted subtrees generating all binary unrooted trees compatible with them, i.e. generating their stand, is one of the classical problems in phylogenetics. Here, we introduce Gentrius-an efficient algorithm to tackle this task. The algorithm has a direct application in practice. Namely, Gentrius generates phylogenetic terraces-topologically distinct, equally scoring trees due to missing data. Despite stand generation being computationally intractable, we showed on simulated and biological datasets that Gentrius generates stands with millions of trees in feasible time. We exemplify that depending on the distribution of missing data across species and loci and the inferred phylogeny, the number of equally optimal terrace trees varies tremendously. The strict consensus tree computed from them displays all the branches unaffected by the pattern of missing data. Thus, by solving the problem of stand generation, in practice Gentrius provides an important systematic assessment of phylogenetic trees inferred from incomplete data. Furthermore, Gentrius can aid theoretical research by fostering understanding of tree space structure imposed by missing data.

Efficient Storage and Analysis of Genomic Data: A k-mer Frequency Mapping and Image Representation Method.

k-mer frequencies are crucial for understanding DNA sequence patterns and structure, with applications in motif discovery, genome classification, and short read assembly. However, the exponential increase in the dimension of frequency tables with increasing k-mer length poses storage challenges. In this study, we present a novel method for compressing k-mer data without information loss, aiming to optimize storage and analysis processes. We employed Chaos Game Representation (CGR) to map k-mers to coordinates and used these components to generate raster images of k-mers. The CGR maps were partitioned and labeled based on substrings, with each substring mapped to a subframe, creating a fractal-like structure. The entire k-mer frequency set of each genomic sequence was represented as a single image, with each pixel corresponding to a specific k-mer and its occurrence. This approach reduced file size by up to 16-fold compared to plain text and 3-fold compared to binary format. Furthermore, we demonstrated the feasibility of performing alignment-free similarity analyses on images derived from k-mer frequencies of whole genome sequences from 14 plant species. Our results highlight the potential of this method as a fast and efficient tool for accessing, processing, and analyzing large biological sequence datasets, enabling the retrieval of k-mer frequencies and image reconstruction.

A clustering ensemble algorithm for handling deep embeddings using cluster confidence

Abstract Clustering ensemble, which aims to learn a robust consensus clustering from multiple weak base clusterings, has achieved promising performance on various applications. With the development of big data, the scale and complexity of data is constantly increasing. However, most existing clustering ensemble methods typically employ shallow clustering algorithms to generate base clusterings. When confronted with high-dimensional complex data, these shallow algorithms fail to fully utilize the intricate features present in the latent data space. As a result, the quality and diversity of the generated base clusterings are insufficient, thus affecting the subsequent ensemble performance. To address this issue, we propose a novel clustering ensemble algorithm for handling deep embeddings using cluster confidence (CEDECC) to improve the robustness and performance. Instead of simply combining deep clustering with clustering ensembles, we take into consideration that the performance of existing deep clustering methods heavily relies on the quality of low-dimensional embeddings generated during the pre-training stage. The quality of embeddings is unstable due to the influence of different initialization parameters. In CEDECC, specifically, we first construct a cluster confidence measure to evaluate the quality of low-dimensional embeddings. Typically, high-quality low-dimensional embeddings yield accurate clustering results with the same model parameters. Then, we utilize multiple high-quality embeddings to generate the base partitions. In the ensemble strategy phase, we consider the cluster-wise diversity and propose a novel ensemble cluster estimation to improve the overall consensus performance of the model. Extensive experiments on three benchmark datasets and four real-world biological datasets have demonstrated that the proposed CEDECC consistently outperforms the state-of-the-art clustering ensemble methods.

Knot data analysis using multiscale Gauss link integral

In the past decade, topological data analysis has emerged as a powerful algebraic topology approach in data science. Although knot theory and related subjects are a focus of study in mathematics, their success in practical applications is quite limited due to the lack of localization and quantization. We address these challenges by introducing knot data analysis (KDA), a paradigm that incorporates curve segmentation and multiscale analysis into the Gauss link integral. The resulting multiscale Gauss link integral (mGLI) recovers the global topological properties of knots and links at an appropriate scale and offers a multiscale geometric topology approach to capture the local structures and connectivities in data. By integration with machine learning or deep learning, the proposed mGLI significantly outperforms other state-of-the-art methods across various benchmark problems in 13 intricately complex biological datasets, including protein flexibility analysis, protein-ligand interactions, human Ether-à-go-go-Related Gene potassium channel blockade screening, and quantitative toxicity assessment. Our KDA opens a research area-knot deep learning-in data science.

Large language models and their applications in bioinformatics

Recent advancements in Natural Language Processing (NLP) have been significantly driven by the development of Large Language Models (LLMs), representing a substantial leap in language-based technology capabilities. These models, built on sophisticated deep learning architectures, typically transformers, are characterized by billions of parameters and extensive training data, enabling them to achieve high accuracy across various tasks. The transformer architecture of LLMs allows them to effectively handle context and sequential information, which is crucial for understanding and generating human language. Beyond traditional NLP applications, LLMs have shown significant promise in bioinformatics, transforming the field by addressing challenges associated with large and complex biological datasets. In genomics, proteomics, and personalized medicine, LLMs facilitate identifying patterns, predicting protein structures, or understanding genetic variations. This capability is crucial, e.g., for advancing drug discovery, where accurate prediction of molecular interactions is essential. This review discusses the current trends in LLMs research and their potential to revolutionize the field of bioinformatics and accelerate novel discoveries in the life sciences.

BioSAM: Generating SAM Prompts From Superpixel Graph for Biological Instance Segmentation.

Proposal-free instance segmentation methods have significantly advanced the field of biological image analysis. Recently, the Segment Anything Model (SAM) has shown an extraordinary ability to handle challenging instance boundaries. However, directly applying SAM to biological images that contain instances with complex morphologies and dense distributions fails to yield satisfactory results. In this work, we propose BioSAM, a new biological instance segmentation framework generating SAM prompts from a superpixel graph. Specifically, to avoid over-merging, we first generate sufficient superpixels as graph nodes and construct an initialized graph. We then generate initial prompts from each superpixel and aggregate them through a graph neural network (GNN) by predicting the relationship of superpixels to avoid over-segmentation. We employ the SAM encoder embeddings and the SAM-assisted superpixel similarity as new features for the graph to enhance its discrimination capability. With the graph-based prompt aggregation, we utilize the aggregated prompts in SAM to refine the segmentation and generate more accurate instance boundaries. Comprehensive experiments on four representative biological datasets demonstrate that our proposed method outperforms state-of-the-art methods.

Potential of quantum machine learning for solving the real-world problem of cancer classification

Quantum machine learning (QML) algorithms have demonstrated the power of quantum computing for solving complex problems and big data in certain tasks. In this study, we explore the capabilities of QML for the classification of real-world biological large datasets including ten different cancer types based on gene expression values. By comparing the classification results obtained from the quantum algorithm with those from classical approaches, we disclose that the QML algorithm overall achieves comparable and reliable results. Moreover, we identify novel biomarkers that can contribute to the understanding of cancer biology. Some of these biomarkers are consistent with DNA promoter methylation. Our findings highlight the potential of QML in cancer classification and biomarker discovery, paving the way for future advancements in other disease research and clinical applications.

Development of AI-assisted microscopy frameworks through realistic simulation with pySTED

The integration of artificial intelligence into microscopy systems significantly enhances performance, optimizing both image acquisition and analysis phases. Development of artificial intelligence-assisted super-resolution microscopy is often limited by access to large biological datasets, as well as by difficulties to benchmark and compare approaches on heterogeneous samples. We demonstrate the benefits of a realistic stimulated emission depletion microscopy simulation platform, pySTED, for the development and deployment of artificial intelligence strategies for super-resolution microscopy. pySTED integrates theoretically and empirically validated models for photobleaching and point spread function generation in stimulated emission depletion microscopy, as well as simulating realistic point-scanning dynamics and using a deep learning model to replicate the underlying structures of real images. This simulation environment can be used for data augmentation to train deep neural networks, for the development of online optimization strategies and to train reinforcement learning models. Using pySTED as a training environment allows the reinforcement learning models to bridge the gap between simulation and reality, as showcased by its successful deployment on a real microscope system without fine tuning.

Cyber-biological convergence: a systematic review and future outlook.

The introduction of the capability to "program" a biological system is referred to as Engineered biology and can be compared to the introduction of the internet and the capability of programming a computer. Engineered biology is supported by a digital infrastructure that includes data, data storage, computer-dependent laboratory equipment, internet-connected communication networks, and supply chains. This connectivity is important. It can improve workflows and enhance productivity. At the same time and unlike computer programs, biological systems introduce unique threats as they can self-assemble, self-repair, and self-replicate. The aim of this paper is to systematically review the cyber implications of engineered biology. This includes cyber-bio opportunities and threats as engineered biology continues to integrate into cyberspace. We used a systematic search methodology to review the academic literature, and supplemented this with a review of opensource materials and "grey" literature that is not disseminated by academic publishers. A comprehensive search of articles published in or after 2017 until the 21st of October 2022 found 52 studies that focus on implications of engineered biology to cyberspace. The search was conducted using search engines that index over 60 databases-databases that specifically cover the information security, and biology literatures, as well as the wider set of academic disciplines. Across these 52 articles, we identified a total of 7 cyber opportunities including automated bio-foundries and 4 cyber threats such as Artificial Intelligence misuse and biological dataset targeting. We highlight the 4 main types of cyberbiosecurity solutions identified in the literature and we suggest a total of 9 policy recommendations that can be utilized by various entities, including governments, to ensure that cyberbiosecurity remains frontline in a growing bioeconomy.

Artificial Intelligence: Future Aspects in the Pharmaceutical Industry an Overview

Artificial intelligence (AI) has emerged as a potent tool leveraging human-like knowledge to offer swift solutions to intricate challenges. Striking advancements in AI technology and machine learning present a revolutionary opportunity in pharmaceutical drug discovery, formulation, and dosage form testing. By employing AI algorithms that scrutinize vast biological datasets encompassing genomics and proteomics, scientists can pinpoint disease-related targets and forecast their interactions with potential drug candidates. This facilitates a more precise and efficient approach to drug discovery, thereby elevating the chances of successful drug approvals. Moreover, AI holds the potential to curtail development costs by streamlining research and development processes. Machine learning algorithms aid in experimental design and can foresee the pharmacokinetics and toxicity of drug candidates, allowing for the prioritization and refinement of lead compounds, thereby reducing the necessity for extensive and expensive animal testing. Personalized medicine initiatives can be advanced through AI algorithms analyzing real-world patient data, culminating in more efficacious treatment outcomes and enhanced patient compliance. This comprehensive overview delves into the diverse applications of AI in pharmaceutical drug discovery, dosage form design for drug delivery, process refinement, testing, and pharmacokinetics/pharmacodynamics (PK/PD) investigations. It provides a glimpse into various AI-driven methodologies employed in pharmaceutical technology, shedding light on their advantages and limitations. Nonetheless, sustained investments in and exploration of AI within the pharmaceutical sector present promising avenues for enhancing drug development processes and patient care.

Noise leads to the perceived increase in evolutionary rates over short time scales.

Across a variety of biological datasets, from genomes to conservation to the fossil record, evolutionary rates appear to increase toward the present or over short time scales. This has long been seen as an indication of processes operating differently at different time scales, even potentially as an indicator of a need for new theory connecting macroevolution and microevolution. Here we introduce a set of models that assess the relationship between rate and time and demonstrate that these patterns are statistical artifacts of time-independent errors present across ecological and evolutionary datasets, which produce hyperbolic patterns of rates through time. We show that plotting a noisy numerator divided by time versus time leads to the observed hyperbolic pattern; in fact, randomizing the amount of change over time generates patterns functionally identical to observed patterns. Ignoring errors can not only obscure true patterns but create novel patterns that have long misled scientists.

Non-equilibrium Statistical Mechanics in Biological Systems

Unlike equilibrium systems, which are characterized by a time-independent distribution of particles and energy, non-equilibrium systems experience constant fluxes of matter or energy, often due to external driving forces. These systems can exhibit a wide range of dynamic behaviors some of which can appear as self-organizing. Building on the framework of non-equilibrium statistical mechanics, Jeremy England in his paper "Statistical Physics of Adaptation" derives an equation which relates the relative forwards probability of transitioning between two possible macrostates with their respective reverse probability, entropy, and average energy dissipation across all possible micro trajectories. He showed that structures which are better at absorbing and dissipating energy into their surroundings during their formation have a higher likelihood of occurring, which can possibly explain how life-like behaviors emerge in non-equilibrium systems. In this project, we test England's equation on a toy model of self replicating populations, as well as attempt to apply it to a biological dataset. In the toy model under certain constraints we do find that our intuition of the systems dynamics does track with England's equation, that is we observe that the population with the greatest replication rate tends to have the highest energy dissipation when it's population makes up the greater fraction of the total population of particles. In the biological dataset we analyze protein-protein interactions and how the relative bonding energy and binding rates compare for different mutations. We explore the limitations of his equation when trying to make predictions about highly complex biological systems.

Sub-sampling graph neural networks for genomic prediction of quantitative phenotypes.

In genomics, use of deep learning (DL) is rapidly growing and DL has successfully demonstrated its ability to uncover complex relationships in large biological and biomedical data sets. With the development of high-throughput sequencing techniques, genomic markers can now be allocated to large sections of a genome. By analysing allele sharing between individuals, one may calculate realized genomic relationships from single nucleotide polymorphisms (SNPs) data rather than relying on known pedigree relationships under polygenic model. The traditional approaches in genome-wide prediction (GWP) of quantitative phenotypes utilise genomic relationships in fixed global covariance modelling, possibly with some non-linear kernel mapping (for example Gaussian processes). On the other hand, the DL approaches proposed so far for GWP fail to take into account the non-Euclidean graph structure of relationships between individuals over several generations. In this paper, we propose one global convolutional neural network (GCN) and one local sub-sampling architecture (GCN-RS) that are specifically designed to perform regression analysis based on genomic relationship information. A GCN is tailored to non-Euclidean spaces and consists of several layers of graph convolutions. The GCN-RS architecture is designed to further improve the GCN's performance by sub-sampling the graph to reduce the dimensionality of the input data. Through these graph convolutional layers, the GCN maps input genomic markers to their quantitative phenotype values. The graphs are constructed using an iterative nearest neighbour approach. Comparisons show that the GCN-RS outperforms the popular Genomic Best Linear Unbiased Predictor (GBLUP) method on one simulated and three real data sets from wheat, mice and pig with a predictive improvement of 4.4% to 49.4% in terms of test mean squared error (MSE). This indicates that GCN-RS is a promising tool for genomic predictions in plants and animals. Furthermore, GCN-RS is computationally efficient, making it a viable option for large-scale applications.

A Novel Method for Targeted Identification of Essential Proteins by Integrating Chemical Reaction Optimization and Naive Bayes Model.

Targeted identification of essential proteins is of great significance for species identification, drug manufacturing, and disease treatment. It is a challenge to analyze the binding mechanism between essential proteins and improve the identification speed while ensuring the accuracy of the identification. This paper proposes a novel method called EPCRO for identifying essential proteins, which incorporates the chemical reaction optimization (CRO) algorithm and the naive Bayes model to effectively detect essential proteins. In EPCRO, the naive Bayes model is employed to analyze the homogeneity between proteins. In order to improve the identification rate and speed of essential proteins, the protein homogeneity rate is integrated into the CRO algorithm to balance between local and global searches. EPCRO is experimentally compared with 17 existing methods (including, DC, SC, IC, EC, LAC, NC, PeC, WDC, EPD-RW, RWHN, TEGS, CFMM, BSPM, AFSO-EP, CVIM, RWEP, and EPPSO-DC) based on biological datasets. The results show that EPCRO is superior to the above methods in identification accuracy and speed.

A hybrid constrained continuous optimization approach for optimal causal discovery from biological data.

Understanding causal effects is a fundamental goal of science and underpins our ability to make accurate predictions in unseen settings and conditions. While direct experimentation is the gold standard for measuring and validating causal effects, the field of causal graph theory offers a tantalizing alternative: extracting causal insights from observational data. Theoretical analysis has shown that this is indeed possible, given a large dataset and if certain conditions are met. However, biological datasets, frequently, do not meet such requirements but evaluation of causal discovery algorithms is typically performed on synthetic datasets, which they meet all requirements. Thus, real-life datasets are needed, in which the causal truth is reasonably known. In this work we first construct such a large-scale real-life dataset and then we perform on it a comprehensive benchmarking of various causal discovery methods. We find that the PC algorithm is particularly accurate at estimating causal structure, including the causal direction which is critical for biological applicability. However, PC does only produces cause-effect directionality, but not estimates of causal effects. We propose PC-NOTEARS (PCnt), a hybrid solution, which includes the PC output as an additional constraint inside the NOTEARS optimization. This approach combines PC algorithm's strengths in graph structure prediction with the NOTEARS continuous optimization to estimate causal effects accurately. PCnt achieved best aggregate performance across all structural and effect size metrics. https://github.com/zhu-yh1/PC-NOTEARS.

A proactive grey wolf optimization for improving bioinformatic systems with high dimensional data

This paper introduces a new methodology for optimization problems, combining the Grey Wolf Optimizer (GWO) with Simi-stochastic search processes. Intelligent optimizations represent an advanced approach in machine learning and computer applications, aiming to reduce the number of features used in the classification process. Optimizing bioinformatics datasets is crucial for information systems that classify data for intelligent tasks. The proposed A-Proactive Grey Wolf Optimization (A-GWO) solves stagnation in GWO by applying a dual search with a Simi-stochastic search. This target is achieved by distributing the population into two groups using a different search technique. The model's performance is evaluated using two benchmarks: the Evolutionary Computation Benchmark (CEC 2005) and seven popular biological datasets. A-GWO demonstrates highly improved efficiency in comparision to the original GWO and Particle Swarm Optimization (PSO). Specifically, it enhances exploration in 66% of CEC functions and achieves high accuracy in 70% of biological datasets.

An Interplay between Transcription Factors and Recombinant Protein Synthesis in Yarrowia lipolytica at Transcriptional and Functional Levels-The Global View.

Transcriptional regulatory networks (TRNs) associated with recombinant protein (rProt) synthesis in Yarrowia lipolytica are still under-described. Yet, it is foreseen that skillful manipulation with TRNs would enable global fine-tuning of the host strain's metabolism towards a high-level-producing phenotype. Our previous studies investigated the transcriptomes of Y. lipolytica strains overproducing biochemically different rProts and the functional impact of transcription factors (TFs) overexpression (OE) on rProt synthesis capacity in this species. Hence, much knowledge has been accumulated and deposited in public repositories. In this study, we combined both biological datasets and enriched them with further experimental data to investigate an interplay between TFs and rProts synthesis in Y. lipolytica at transcriptional and functional levels. Technically, the RNAseq datasets were extracted and re-analyzed for the TFs' expression profiles. Of the 140 TFs in Y. lipolytica, 87 TF-encoding genes were significantly deregulated in at least one of the strains. The expression profiles were juxtaposed against the rProt amounts from 125 strains co-overexpressing TF and rProt. In addition, several strains bearing knock-outs (KOs) in the TF loci were analyzed to get more insight into their actual involvement in rProt synthesis. Different profiles of the TFs' transcriptional deregulation and the impact of their OE or KO on rProts synthesis were observed, and new engineering targets were pointed.