pwc-archive/papers-with-abstracts huggingface dataset:
Exploring zero-shot structure-based protein fitness prediction
Authors: Arnav Sharma, Anthony Gitter
Date: 2025-04-23 00:00:00
Tasks: Prediction, Protein Structure Prediction

The ability to make zero-shot predictions about the fitness consequences of protein sequence changes with pre-trained machine learning models enables many practical applications. Such models can be applied for downstream tasks like genetic variant interpretation and protein engineering without additional labeled data. The advent of capable protein structure prediction tools has led to the availability of orders of magnitude more precomputed predicted structures, giving rise to powerful structure-based fitness prediction models. Through our experiments, we assess several modeling choices for structure-based models and their effects on downstream fitness prediction. Zero-shot fitness prediction models can struggle to assess the fitness landscape within disordered regions of proteins, those that lack a fixed 3D structure. We confirm the importance of matching protein structures to fitness assays and find that predicted structures for disordered regions can be misleading and affect predictive performance. Lastly, we evaluate an additional structure-based model on the ProteinGym substitution benchmark and show that simple multi-modal ensembles are strong baselines.
The Dance of Atoms-De Novo Protein Design with Diffusion Model
Authors: Yujie Qin, Ming He, Changyong Yu, Ming Ni, Xian Liu, Xiaochen Bo
Date: 2025-04-23 00:00:00
Tasks: Hallucination, Protein Design

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological advancements have paved the way for the successful application of generative artificial intelligence (AI) models in protein design. These models have surpassed traditional approaches that rely on fragments and bioinformatics. They have significantly enhanced the success rate of de novo protein design, and reduced experimental costs, leading to breakthroughs in the field. Among various generative AI models, diffusion models have yielded the most promising results in protein design. In the past two to three years, more than ten protein design models based on diffusion models have emerged. Among them, the representative model, RFDiffusion, has demonstrated success rates in 25 protein design tasks that far exceed those of traditional methods, and other AI-based approaches like RFjoint and hallucination. This review will systematically examine the application of diffusion models in generating protein backbones and sequences. We will explore the strengths and limitations of different models, summarize successful cases of protein design using diffusion models, and discuss future development directions.
Heterogeneous networks in drug-target interaction prediction
Authors: Mohammad Molaee, Nasrollah Moghadam Charkari, Foad Ghaderi
Date: 2025-04-22 00:00:00
Tasks: Drug Discovery, Prediction

Drug discovery requires a tremendous amount of time and cost. Computational drug-target interaction prediction, a significant part of this process, can reduce these requirements by narrowing the search space for wet lab experiments. In this survey, we provide comprehensive details of graph machine learning-based methods in predicting drug-target interaction, as they have shown promising results in this field. These details include the overall framework, main contribution, datasets, and their source codes. The selected papers were mainly published from 2020 to 2024. Prior to discussing papers, we briefly introduce the datasets commonly used with these methods and measurements to assess their performance. Finally, future challenges and some crucial areas that need to be explored are discussed.
Functional Amyloid Fibrils as Versatile Tools for Novel Biomaterials
Authors: Shayan Mortazavi, Mehrnoosh Neshatian, Laurent Bozec, Hadis Zarrin, Mahshid Kalani
Date: 2025-04-22 00:00:00

Functional amyloid fibrils, once primarily associated with amyloidosis, are now recognized for their exceptional potential as biomaterials due to their unique structural features, including remarkable mechanical strength, high stability, and self-assembly capabilities. This review highlights their transformative applications across a wide range of industries, from cutting-edge drug delivery systems and next-generation biosensors to tissue engineering, surface technologies, energy storage, and environmental solutions. Their versatility extends into innovative sectors like information transfer systems, cell adhesion, protein fusion, food technology, and novel catalytic systems. Despite significant progress, critical gaps remain in the research. This review not only consolidates current applications but also underscores the vast potential for future advancements, positioning functional amyloids as key players in emerging biomaterials technologies.
From sequence to protein structure and conformational dynamics with AI/ML
Authors: Alexander M. Ille, Emily Anas, Michael B. Mathews, Stephen K. Burley
Date: 2025-04-18 00:00:00
Tasks: Protein Structure Prediction

The 2024 Nobel Prize in Chemistry was awarded in part for protein structure prediction using AlphaFold2, an artificial intelligence/machine learning (AI/ML) model trained on vast amounts of sequence and 3D structure data. AlphaFold2 and related models, including RoseTTAFold and ESMFold, employ specialized neural network architectures driven by attention mechanisms to infer relationships between sequence and structure. At a fundamental level, these AI/ML models operate on the long-standing hypothesis that the structure of a protein is determined by its amino acid sequence. More recently, AlphaFold2 has been adapted for the prediction of multiple protein conformations by subsampling multiple sequence alignments (MSAs). The deterministic relationship between sequence and structure was hypothesized over half a century ago with profound implications for the biological sciences ever since. Based on this relationship, we hypothesize that protein conformational dynamics are also determined, at least in part, by amino acid sequence and that this relationship may be leveraged for construction of AI/ML models dedicated to predicting ensembles of protein structures (i.e., distinct conformations). Accordingly, we conceptualized an AI/ML model architecture which may be trained on sequence data in combination with conformationally-sensitive structure data, coming primarily from nuclear magnetic resonance (NMR) spectroscopy. Sequence-informed prediction of protein structural dynamics has the potential to emerge as a transformative capability across the biological sciences, and its implementation could very well be on the horizon.
p2smi: A Python Toolkit for Peptide FASTA-to-SMILES Conversion and Molecular Property Analysis
Authors: Aaron L. Feller, Claus O. Wilke
Date: 2025-04-18 00:00:00

Converting peptide sequences into useful representations for downstream analysis is a common step in computational modeling and cheminformatics. Furthermore, peptide drugs (e.g., Semaglutide, Degarelix) often take advantage of the diverse chemistries found in noncanonical amino acids (NCAAs), altered stereochemistry, and backbone modifications. Despite there being several chemoinformatics toolkits, none are tailored to the task of converting a modified peptide from an amino acid representation to the chemical string nomenclature Simplified Molecular-Input Line-Entry System (SMILES), often used in chemical modeling. Here we present p2smi, a Python toolkit with CLI, designed to facilitate the conversion of peptide sequences into chemical SMILES strings. By supporting both cyclic and linear peptides, including those with NCAAs, p2smi enables researchers to generate accurate SMILES strings for drug-like peptides, reducing the overhead for computational modeling and cheminformatics analyses. The toolkit also offers functionalities for chemical modification, synthesis feasibility evaluation, and calculation of molecular properties such as hydrophobicity, topological polar surface area, molecular weight, and adherence to Lipinski's rules for drug-likeness.
An X-ray absorption spectrum database for iron-containing proteins
Authors: Yufeng Wang, Peiyao Wang, Emerita Mendoza Rengifo, Dali Yang, Keying Jia, Rutwik Segireddy, Lu Ma, Yuewei Lin, Qun Liu, Haibin Ling
Date: 2025-04-14 00:00:00

Earth-abundant iron is an essential metal in regulating the structure and function of proteins. This study presents the development of a comprehensive X-ray Absorption Spectroscopy (XAS) database focused on iron-containing proteins, addressing a critical gap in available high-quality annotated spectral data for iron-containing proteins. The database integrates detailed XAS spectra with their corresponding local structural data of proteins and enables a direct comparison of spectral features and structural motifs. Utilizing a combination of manual curation and semi-automated data extraction techniques, we developed a comprehensive dataset from an extensive review of literature, ensuring the quality and accuracy of data, which contains 437 protein structures and 1954 XAS spectrums. Our methods included careful documentation and validation processes to ensure accuracy and reproducibility. This dataset not only centralizes information on iron-containing proteins but also supports advanced data-driven discoveries, such as machine learning, to predict and analyze protein structure and functions. This work underscores the potential of integrating detailed spectroscopic data with structural biology to advance the field of biological chemistry and catalysis.
GenShin:geometry-enhanced structural graph embodies binding pose can better predicting compound-protein interaction affinity
Authors: Pingfei Zhu, Chenyang Zhao, Haishi Zhao, Bo Yang
Date: 2025-03-16 00:00:00
Tasks: Drug Design, Drug Discovery

AI-powered drug discovery typically relies on the successful prediction of compound-protein interactions, which are pivotal for the evaluation of designed compound molecules in structure-based drug design and represent a core challenge in the field. However, accurately predicting compound-protein affinity via regression models usually requires adequate-binding pose, which are derived from costly and complex experimental methods or time-consuming simulations with docking software. In response, we have introduced the GenShin model, which constructs a geometry-enhanced structural graph module that separately extracts additional features from proteins and compounds. Consequently, it attains an accuracy on par with mainstream models in predicting compound-protein affinities, while eliminating the need for adequate-binding pose as input. Our experimental findings demonstrate that the GenShin model vastly outperforms other models that rely on non-input docking conformations, achieving, or in some cases even exceeding, the performance of those requiring adequate-binding pose. Further experiments indicate that our GenShin model is more robust to inadequate-binding pose, affirming its higher suitability for real-world drug discovery scenarios. We hope our work will inspire more endeavors to bridge the gap between AI models and practical drug discovery challenges.
Using mathematical models of heart cells to assess the safety of new pharmaceutical drugs
Authors: Gary R. Mirams
Date: 2025-04-24 00:00:00
Tasks: Blocking, Rhythm

Many drugs have been withdrawn from the market worldwide, at a cost of billions of dollars, because of patient fatalities due to them unexpectedly disturbing heart rhythm. Even drugs for ailments as mild as hay fever have been withdrawn due to an unacceptable increase in risk of these heart rhythm disturbances. Consequently, the whole pharmaceutical industry expends a huge effort in checking all new drugs for any unwanted side effects on the heart. The predominant root cause has been identified as drug molecules blocking ionic current flows in the heart. Block of individual types of ionic currents can now be measured experimentally at an early stage of drug development, and this is the standard screening approach for a number of ion currents in many large pharmaceutical companies. However, clinical risk is a complex function of the degree of block of many different types of cardiac ion currents, and this is difficult to understand by looking at results of these screens independently. By using ordinary differential equation models for the electrical activity of heart cells (electrophysiology models) we can integrate information from different types of currents, to predict the effect on whole heart cells and subsequent risk of side effects. The resulting simulations can provide a more accurate summary of the risk of a drug earlier in development and hence more cheaply than the pre-existing approaches.
Quantitative Analysis of Cell Membrane Tension in Time-Series Imaging and A Minimal Lattice Model of Single Cell Motion
Authors: Hiroki Nishitani, Takashi Miura
Date: 2025-04-21 00:00:00
Tasks: Time Series

Cell membrane tension directly influences various cellular functions. In this study, we developed a method to estimate surface tension from time-series data. We obtained the curvature-velocity relationship from time-series of binarized cell shape images, and the effective surface tension term was calculated from linear regression. During the process, we observed an S-shaped pattern in the curvature-velocity relationship. To understand the dynamics, we constructed a minimal lattice model describing single-cell motion. The model consists of surface tension and protrusion formation, and the characteristic parameters are obtained from experimental observations. We found that similar patterns emerged in the curvature-velocity relationship.
Gene finding revisited: improved robustness through structured decoding from learned embeddings
Authors: Frederikke I. Marin, Dennis Pultz, Wouter Boomsma
Date: 2025-05-06 00:00:00
Tasks: Representation Learning

Gene finding is the task of identifying the locations of coding sequences within the vast amount of genetic code contained in the genome. With an ever increasing quantity of raw genome sequences, gene finding is an important avenue towards understanding the genetic information of (novel) organisms, as well as learning shared patterns across evolutionarily diverse species. The current state of the art are graphical models usually trained per organism and requiring manually curated datasets. However, these models lack the flexibility to incorporate deep learning representation learning techniques that have in recent years been transformative in the analysis of pro tein sequences, and which could potentially help gene finders exploit the growing number of the sequenced genomes to expand performance across multiple organisms. Here, we propose a novel approach, combining learned embeddings of raw genetic sequences with exact decoding using a latent conditional random field. We show that the model achieves performance matching the current state of the art, while increasing training robustness, and removing the need for manually fitted length distributions. As language models for DNA improve, this paves the way for more performant cross-organism gene-finders.
OmicsCL: Unsupervised Contrastive Learning for Cancer Subtype Discovery and Survival Stratification
Authors: Atahan Karagoz
Date: 2025-05-01 00:00:00
Tasks: Contrastive Learning

Unsupervised learning of disease subtypes from multi-omics data presents a significant opportunity for advancing personalized medicine. We introduce OmicsCL, a modular contrastive learning framework that jointly embeds heterogeneous omics modalities-such as gene expression, DNA methylation, and miRNA expression-into a unified latent space. Our method incorporates a survival-aware contrastive loss that encourages the model to learn representations aligned with survival-related patterns, without relying on labeled outcomes. Evaluated on the TCGA BRCA dataset, OmicsCL uncovers clinically meaningful clusters and achieves strong unsupervised concordance with patient survival. The framework demonstrates robustness across hyperparameter configurations and can be tuned to prioritize either subtype coherence or survival stratification. Ablation studies confirm that integrating survival-aware loss significantly enhances the predictive power of learned embeddings. These results highlight the promise of contrastive objectives for biological insight discovery in high-dimensional, heterogeneous omics data.
A Bioinformatic Study of Genetics Involved in Determining Mild Traumatic Brain Injury Severity and Recovery
Authors: Mahnaz Tajik, Michael D Noseworthy
Date: 2025-05-01 00:00:00

Aim: This in silico study sought to identify specific biomarkers for mild traumatic brain injury (mTBI) through the analysis of publicly available gene and miRNA databases, hypothesizing their influence on neuronal structure, axonal integrity, and regeneration. Methods: This study implemented a three-step process: (1) Data searching for mTBI-related genes in Gene and MalaCard databases and literature review ; (2) Data analysis involved performing functional annotation through GO and KEGG, identifying hub genes using Cytoscape, mapping protein-protein interactions via DAVID and STRING, and predicting miRNA targets using miRSystem, miRWalk2.0, and mirDIP (3) RNA-sequencing analysis applied to the mTBI dataset GSE123336. Results: Eleven candidate hub genes associated with mTBI outcome were identified: APOE, S100B, GFAP, BDNF, AQP4, COMT, MBP, UCHL1, DRD2, ASIC1, and CACNA1A. Enrichment analysis linked these genes to neuron projection regeneration and synaptic plasticity. miRNAs linked to the mTBI candidate genes were hsa-miR-9-5p, hsa-miR-204-5p, hsa-miR-1908-5p, hsa-miR-16-5p, hsa-miR-10a-5p, has-miR-218-5p, has-miR-34a-5p, and has-miR-199b-5p. The RNA sequencing revealed 2664 differentially expressed miRNAs post-mTBI, with 17 showing significant changes at the time of injury and 48 hours post-injury. Two miRNAs were positively correlated with direct head hits. Conclusion: Our study indicates that specific genes and miRNAs, particularly hsa-miR-10a-5p, may influence mTBI outcomes. Our research may guide future mTBI diagnostics, emphasizing the need to measure and track these specific genes and miRNAs in diverse cohorts.
Mantodea phylogenomics provides new insights into X-chromosome progression and evolutionary radiation
Authors: Hangwei Liu, Lihong Lei, Fan Jiang, Bo Zhang, Hengchao Wang, Yutong Zhang, Anqi Wang, Hanbo Zhao, Guirong Wang, Wei Fan
Date: 2025-04-29 00:00:00

Background: Praying mantises, members of the order Mantodea, play important roles in agriculture, medicine, bionics, and entertainment. However, the scarcity of genomic resources has hindered extensive studies on mantis evolution and behaviour. Results: Here, we present the chromosome-scale reference genomes of five mantis species: the European mantis (Mantis religiosa), Chinese mantis (Tenodera sinensis), triangle dead leaf mantis (Deroplatys truncata), orchid mantis (Hymenopus coronatus), and metallic mantis (Metallyticus violaceus). We found that transposable element expansion is the major force governing genome size in Mantodea. Based on whole-alignments, we deduced that the Mantodea ancestor may have had only one X chromosome and that translocations between the X chromosome and an autosome may have occurred in the lineage of the superfamily Mantoidea. Furthermore, we found a lower evolutionary rate for the metallic mantis than for the other mantises. We also found that Mantodea underwent rapid radiation after the K-Pg mass extinction event, which could have contributed to the confusion in species classification. Conclusions: We present the chromosome-scale reference genomes of five mantis species to reveal the X-chromosome evolution, clarify the phylogeny relationship, and transposable element expansion.
An Integrated Genomics Workflow Tool: Simulating Reads, Evaluating Read Alignments, and Optimizing Variant Calling Algorithms
Authors: Fathima Nuzla Ismail, Shanika Amarasoma
Date: 2025-04-24 00:00:00

Next-generation sequencing (NGS) is a pivotal technique in genome sequencing due to its high throughput, rapid results, cost-effectiveness, and enhanced accuracy. Its significance extends across various domains, playing a crucial role in identifying genetic variations and exploring genomic complexity. NGS finds applications in diverse fields such as clinical genomics, comparative genomics, functional genomics, and metagenomics, contributing substantially to advancements in research, medicine, and scientific disciplines. Within the sphere of genomics data science, the execution of read simulation, mapping, and variant calling holds paramount importance for obtaining precise and dependable results. Given the plethora of tools available for these purposes, each employing distinct methodologies and options, a nuanced understanding of their intricacies becomes imperative for optimization. This research, situated at the intersection of data science and genomics, involves a meticulous assessment of various tools, elucidating their individual strengths and weaknesses through rigorous experimentation and analysis. This comprehensive evaluation has enabled the researchers to pinpoint the most accurate tools, reinforcing the alignment between the established workflow and the demonstrated efficacy of specific tools in the context of genomics data analysis. To meet these requirements, "VarFind", an open-source and freely accessible pipeline tool designed to automate the entire process has been introduced (VarFind GitHub repository: https://github.com/shanikawm/varfinder)
A Comprehensive Review on RNA Subcellular Localization Prediction
Authors: Cece Zhang, Xuehuan Zhu, Nick Peterson, Jieqiong Wang, Shibiao Wan
Date: 2025-04-24 00:00:00
Tasks: Prediction

The subcellular localization of RNAs, including long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), microRNAs (miRNAs) and other smaller RNAs, plays a critical role in determining their biological functions. For instance, lncRNAs are predominantly associated with chromatin and act as regulators of gene transcription and chromatin structure, while mRNAs are distributed across the nucleus and cytoplasm, facilitating the transport of genetic information for protein synthesis. Understanding RNA localization sheds light on processes like gene expression regulation with spatial and temporal precision. However, traditional wet lab methods for determining RNA localization, such as in situ hybridization, are often time-consuming, resource-demanding, and costly. To overcome these challenges, computational methods leveraging artificial intelligence (AI) and machine learning (ML) have emerged as powerful alternatives, enabling large-scale prediction of RNA subcellular localization. This paper provides a comprehensive review of the latest advancements in AI-based approaches for RNA subcellular localization prediction, covering various RNA types and focusing on sequence-based, image-based, and hybrid methodologies that combine both data types. We highlight the potential of these methods to accelerate RNA research, uncover molecular pathways, and guide targeted disease treatments. Furthermore, we critically discuss the challenges in AI/ML approaches for RNA subcellular localization, such as data scarcity and lack of benchmarks, and opportunities to address them. This review aims to serve as a valuable resource for researchers seeking to develop innovative solutions in the field of RNA subcellular localization and beyond.