How healthy am I? My immunome knows the score. Groundbreaking new tests reveal patterns in our immune systems that can signal underlying disease and tell us how well we might recover from our next cold. I got my results in a text message. It's not often you get a text about the robustness of your immune system, but that's what popped up on my phone last spring. Sent by John Tsang, an immunologist at Yale, the text came after his lab had put my blood through a mind-boggling array of newfangled tests. The result--think of it as a full-body, high-resolution CT scan of my immune system--would reveal more about the state of my health than any test I had ever taken. And it could potentially tell me far more than I wanted to know. "David," the text read, "you are the red dot." Tsang was referring to an image he had attached to the text that showed a graph with a scattering of black dots representing other people whose immune systems had been evaluated--and a lone red one.

Machine and deep learning have grown in popularity and use in biological research over the last decade but still present challenges in interpretability of the fitted model. The development and use of metrics to determine features driving predictions and increase model i nterpretability continues to be an open area of research. We investigate the use of Shapley Additive Explanations (SHAP) on a multi - view deep learning model applied to multi - omics data for the purposes of identifying biomolecules of interest . Rankings of features via these attribution methods are compared across various architectures to evaluate consistency of the method. We perform multiple computational experiments to assess the robustness of SHAP and investigate modeling approaches and diagnostics to increase and measure the reliability of the identification of important features. Accuracy of a random - forest model fit on subsets of features selected as being most influential as well as clustering quality using o nly these features are used as a measure of enullectiveness of the attribution method. Our findings indicate that the rankings of features resulting from SHAP are sensitive to the choice of architecture as well as dinullerent random initializations of weights, suggesting caution when u sing attribution methods on multi - view deep learning models applied to multi - omics data. We present a n alternative, simple method to assess the robustness of identification of important biomolecules.

The search for evidence of past life on Mars presents a tremendous challenge that requires the usage of very advanced robotic technologies to overcome it. Current digital microscopic imagers and spectrometers used for astrobiological examination suffer from limitations such as insufficient resolution, narrow detection range, and lack of portability. To overcome these challenges, this research study presents modifications to the Phoenix rover to expand its capability for detecting biosignatures on Mars. This paper examines the modifications implemented on the Phoenix rover to enhance its capability to detect a broader spectrum of biosignatures. One of the notable improvements comprises the integration of advanced digital microscopic imagers and spectrometers, enabling high-resolution examination of soil samples. Additionally, the mechanical components of the device have been reinforced to enhance maneuverability and optimize subsurface sampling capabilities. Empirical investigations have demonstrated that Phoenix has the capability to navigate diverse geological environments and procure samples for the purpose of biomolecular analysis. The biomolecular instrumentation and hybrid analytical methods showcased in this study demonstrate considerable potential for future astrobiology missions on Mars. The potential for enhancing the system lies in the possibility of broadening the range of detectable biomarkers and biosignatures.

During the early stages of respiratory virus outbreaks, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the efficient utilize of limited nasopharyngeal swabs for rapid and accurate screening is crucial for public health. In this study, we present a methodology that integrates attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) with the adaptive iteratively reweighted penalized least squares (airPLS) preprocessing algorithm and a channel-wise attention-based partial least squares one-dimensional convolutional neural network (PLS-1D-CNN) model, enabling accurate screening of infected individuals within 10 minutes. Two cohorts of nasopharyngeal swab samples, comprising 126 and 112 samples from suspected SARS-CoV-2 Omicron variant cases, were collected at Beijing You'an Hospital for verification. Given that ATR-FTIR spectra are highly sensitive to variations in experimental conditions, which can affect their quality, we propose a biomolecular importance (BMI) evaluation method to assess signal quality across different conditions, validated by comparing BMI with PLS-GBM and PLS-RF results. For the ATR-FTIR signals in cohort 2, which exhibited a higher BMI, airPLS was utilized for signal preprocessing, followed by the application of the channel-wise attention-based PLS-1D-CNN model for screening. The experimental results demonstrate that our model outperforms recently reported methods in the field of respiratory virus spectrum detection, achieving a recognition screening accuracy of 96.48%, a sensitivity of 96.24%, a specificity of 97.14%, an F1-score of 96.12%, and an AUC of 0.99. It meets the World Health Organization (WHO) recommended criteria for an acceptable product: sensitivity of 95.00% or greater and specificity of 97.00% or greater for testing prior SARS-CoV-2 infection in moderate to high volume scenarios.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

Diffusion probabilistic models have made their way into a number of high-profile applications since their inception. In particular, there has been a wave of research into using diffusion models in the prediction and design of biomolecular structures and sequences. Their growing ubiquity makes it imperative for researchers in these fields to understand them. This paper serves as a general overview for the theory behind these models and the current state of research. We first introduce diffusion models and discuss common motifs used when applying them to biomolecules. We then present the significant outcomes achieved through the application of these models in generative and predictive tasks. This survey aims to provide readers with a comprehensive understanding of the increasingly critical role of diffusion models.

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in \url{https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling}.

Spatial omics refers to the ability to measure the activity of biomolecules (RNA, DNA, proteins, and other omics) in situ--directly from tissue samples. This is important because many biological processes are controlled by highly localized interactions between cells that take place in spatially heterogeneous tissue environments. Spatial omics allows previously unobservable cellular organization and biological events to be viewed in unprecedented detail. A few years ago, these technologies were just prototypes in a handful of labs around the world. They worked only on frozen tissue and they required impractically large amounts of precious tissue biopsies.

Large Language Models (LLMs), with their remarkable task-handling capabilities and innovative outputs, have catalyzed significant advancements across a spectrum of fields. However, their proficiency within specialized domains such as biomolecular studies remains limited. To address this challenge, we introduce Mol-Instructions, a comprehensive instruction dataset designed for the biomolecular domain. Mol-Instructions encompasses three key components: molecule-oriented instructions, protein-oriented instructions, and biomolecular text instructions. Each component aims to improve the understanding and prediction capabilities of LLMs concerning biomolecular features and behaviors. Through extensive instruction tuning experiments on LLMs, we demonstrate the effectiveness of Mol-Instructions in enhancing large models' performance in the intricate realm of biomolecular studies, thus fostering progress in the biomolecular research community. Mol-Instructions is publicly available for ongoing research and will undergo regular updates to enhance its applicability.

Molecular representation learning (MRL) is a powerful tool for bridging the gap between machine learning and chemical sciences, as it converts molecules into numerical representations while preserving their chemical features. These encoded representations serve as a foundation for various downstream biochemical studies, including property prediction and drug design. MRL has had great success with proteins and general biomolecule datasets. Yet, in the growing sub-field of glycoscience (the study of carbohydrates, where longer carbohydrates are also called glycans), MRL methods have been barely explored. This under-exploration can be primarily attributed to the limited availability of comprehensive and well-curated carbohydrate-specific datasets and a lack of Machine learning (ML) pipelines specifically tailored to meet the unique problems presented by carbohydrate data. Since interpreting and annotating carbohydrate-specific data is generally more complicated than protein data, domain experts are usually required to get involved. The existing MRL methods, predominately optimized for proteins and small biomolecules, also cannot be directly used in carbohydrate applications without special modifications. To address this challenge, accelerate progress in glycoscience, and enrich the data resources of the MRL community, we introduce GlycoNMR. GlycoNMR contains two laboriously curated datasets with 2,609 carbohydrate structures and 211,543 annotated nuclear magnetic resonance (NMR) chemical shifts for precise atomic-level prediction. We tailored carbohydrate-specific features and adapted existing MRL models to tackle this problem effectively. For illustration, we benchmark four modified MRL models on our new datasets.