Artificial intelligence (AI) is transforming scientific research, including proteomics. Advances in mass spectrometry (MS)-based proteomics data quality, diversity, and scale, combined with groundbreaking AI techniques, are unlocking new challenges and opportunities in biological discovery. Here, we highlight key areas where AI is driving innovation, from data analysis to new biological insights. These include developing an AI-friendly ecosystem for proteomics data generation, sharing, and analysis; improving peptide and protein identification and quantification; characterizing protein-protein interactions and protein complexes; advancing spatial and perturbation proteomics; integrating multi-omics data; and ultimately enabling AI-empowered virtual cells.

Protein-ligand binding [Clyde et al., 2023] refers to the process as shown in Figure 1 by which ligands--usually small molecules, ions, or proteins--generate signals by binding to the active sites of target proteins through intermolecular forces. This binding typically changes the conformation of target proteins, which then results in the realization, modulation, or alteration of protein functions. Therefore, protein-ligand binding plays a central role in most, if not all, important life processes. For example, oxygen molecules are bound and carried through the human body by proteins like hemoglobin, and then utilized for energy production, while nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen work by inhibiting the functionality of the cyclooxygenase (COX) enzyme that thus reducing the release of pain-causing substances in the body. The concept and importance of binding affinity prediction were first addressed in Böhm [1994]: given the 3D structures of a target protein and a potential ligand, the objective is to predict the binding constant of such a complex, along with the most probable binding pose candidates. The prediction of the binding site (the set of protein residues that have at least one non-hydrogen atom within 4.0 Å of a ligand's non-hydrogen atom [Khazanov and Carlson, 2013]) and affinity (binding constants such as inhibition or dissociation constants, or the concentration at 50% inhibition) are usually divided into two separate but related stages [Ballester and Mitchell, 2010a]. One notable motivation for constructing a good binding affinity predictor (or scoring function, as called in some earlier work) is the essential role that it plays in drug discovery [Liu et al., 2023, 2024a] and virtual screening [Meng et al., 2011, Pinzi and Rastelli, 2019, Sadybekov and Katritch, 2023]. Traditional drug discovery essentially involves a process of trial and error.

Computing in the life sciences has undergone a transformative evolution, from early computational models in the 1950s to the applications of arti cial intelligence (AI) and machine learning (ML) seen today. This paper highlights key milestones and technological advancements through the historical development of computing in the life sciences. The discussion includes the inception of computational models for biological processes, the advent of bioinformatics tools, and the integration of AI/ML in modern life sciences research. Attention is given to AI-enabled tools used in the life sciences, such as scienti c large language models and bio-AI tools, examining their capabilities, limitations, and impact to biological risk. This paper seeks to clarify and establish essential terminology and concepts to ensure informed decision-making and e ective communication across disciplines. The views and opinions expressed within this manuscript are those of the authors and do not necessarily re ect the views and opinions of any organization the authors are a liated with.

The process of identifying a compound from its mass spectrum is a critical step in the analysis of complex mixtures. Typical solutions for the mass spectrum to compound (MS2C) problem involve matching the unknown spectrum against a library of known spectrum-molecule pairs, an approach that is limited by incomplete library coverage. Compound to mass spectrum (C2MS) models can improve retrieval rates by augmenting real libraries with predicted spectra. Unfortunately, many existing C2MS models suffer from problems with prediction resolution, scalability, or interpretability. We develop a new probabilistic method for C2MS prediction, FraGNNet, that can efficiently and accurately predict high-resolution spectra. FraGNNet uses a structured latent space to provide insight into the underlying processes that define the spectrum. Our model achieves state-of-the-art performance in terms of prediction error, and surpasses existing C2MS models as a tool for retrieval-based MS2C.

In this chapter we illustrate the use of some Machine Learning techniques in the context of omics data. More precisely, we review and evaluate the use of Random Forest and Penalized Multinomial Logistic Regression for integrative analysis of genomics and immunomics in pancreatic cancer. Furthermore, we propose the use of association rules with predictive purposes to overcome the low predictive power of the previously mentioned models. Finally, we apply the reviewed methods to a real data set from TCGA made of 107 tumoral pancreatic samples and 117,486 germline SNPs, showing the good performance of the proposed methods to predict the immunological infiltration in pancreatic cancer.

Tandem mass spectra capture fragmentation patterns that provide key structural information about a molecule. Although mass spectrometry is applied in many areas, the vast majority of small molecules lack experimental reference spectra. For over seventy years, spectrum prediction has remained a key challenge in the field. Existing deep learning methods do not leverage global structure in the molecule, potentially resulting in difficulties when generalizing to new data. In this work we propose a new model, MassFormer, for accurately predicting tandem mass spectra. MassFormer uses a graph transformer architecture to model long-distance relationships between atoms in the molecule. The transformer module is initialized with parameters obtained through a chemical pre-training task, then fine-tuned on spectral data. MassFormer outperforms competing approaches for spectrum prediction on multiple datasets, and is able to recover prior knowledge about the effect of collision energy on the spectrum. By employing gradient-based attribution methods, we demonstrate that the model can identify relationships between fragment peaks. To further highlight MassFormer's utility, we show that it can match or exceed existing prediction-based methods on two spectrum identification tasks. We provide open-source implementations of our model and baseline approaches, with the goal of encouraging future research in this area.

Cytometry enables precise single-cell phenotyping within heterogeneous populations. These cell types are traditionally annotated via manual gating, but this method suffers from a lack of reproducibility and sensitivity to batch-effect. Also, the most recent cytometers - spectral flow or mass cytometers - create rich and high-dimensional data whose analysis via manual gating becomes challenging and time-consuming. To tackle these limitations, we introduce Scyan (https://github.com/MICS-Lab/scyan), a Single-cell Cytometry Annotation Network that automatically annotates cell types using only prior expert knowledge about the cytometry panel. We demonstrate that Scyan significantly outperforms the related state-of-the-art models on multiple public datasets while being faster and interpretable. In addition, Scyan overcomes several complementary tasks such as batch-effect removal, debarcoding, and population discovery. Overall, this model accelerates and eases cell population characterisation, quantification, and discovery in cytometry.

Quantum computing has gained a lot of attention recently, and scientists have seen potential applications in this field using quantum computing for Cryptography and Communication to Machine Learning and Healthcare. Protein folding has been one of the most interesting areas to study, and it is also one of the biggest problems of biochemistry. Each protein folds distinctively, and the difficulty of finding its stable shape rapidly increases with an increase in the number of amino acids in the chain. A moderate protein has about 100 amino acids, and the number of combinations one needs to verify to find the stable structure is enormous. At some point, the number of these combinations will be so vast that classical computers cannot even attempt to solve them. In this paper, we examine how this problem can be solved with the help of quantum computing using two different algorithms, Variational Quantum Eigensolver (VQE) and Quantum Approximate Optimization Algorithm (QAOA), using Qiskit Nature. We compare the results of different quantum hardware and simulators and check how error mitigation affects the performance. Further, we make comparisons with SoTA algorithms and evaluate the reliability of the method.

Nowadays there is a big spotlight cast on the development of techniques of explainable machine learning. Here we introduce a new computational paradigm based on Group Equivariant Non-Expansive Operators, that can be regarded as the product of a rising mathematical theory of information-processing observers. This approach, that can be adjusted to different situations, may have many advantages over other common tools, like Neural Networks, such as: knowledge injection and information engineering, selection of relevant features, small number of parameters and higher transparency. We chose to test our method, called GENEOnet, on a key problem in drug design: detecting pockets on the surface of proteins that can host ligands. Experimental results confirmed that our method works well even with a quite small training set, providing thus a great computational advantage, while the final comparison with other state-of-the-art methods shows that GENEOnet provides better or comparable results in terms of accuracy.

ENR New York is pleased to announce this year's regional Contractor of the Year: Gilbane Building Company! The following are a few reasons for the firm's selection, and we'll publish a comprehensive feature on the company in the July issue of ENR New York and New England. In 2020, Gilbane celebrated its 150th anniversary, having transformed from a two-man carpentry start-up in Rhode Island into a global firm with a full slate of construction and facilities-related services. During the pandemic, the company's New York regional revenue reached $1.56 billion, an increase from $1.49 billion a year earlier. The firm also says its overall revenue reached an all-time high of $6.5 billion in 2020.