Using Unsupervised Machine Learning to Predict Quality of Life After Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) are an important metric to assess total knee arthroplasty (TKA) patients. The purpose of this study was to use a machine learning (ML) algorithm to identify patient features that impact PROMs after TKA. METHODS: Data from 636 TKA patients enrolled in our patient database between 2018 and 2022, were retrospectively reviewed. Their mean age was 68 years (range, 39 to 92), 56.7% women, and mean body mass index of 31.17 (range, 16 to 58). Patient demographics and the Functional Comorbidity Index were collected alongside Patient-Reported Outcome Measures Information System Global Health v1.2 (PROMIS GH-P) physical component scores preoperatively, at 3 months, and 1 year after TKA. An unsupervised ML algorithm (spectral clustering) was used to identify patient features impacting PROMIS GH-P scores at the various time points. RESULTS: The algorithm identified 5 patient clusters that varied by demographics, comorbidities, and pain scores. Each cluster was associated with predictable trends in PROMIS GH-P scores across the time points. Notably, patients who had the worst preoperative PROMIS GH-P scores (cluster 5) had the most improvement after TKA, whereas patients who had higher global health rating preoperatively had more modest improvement (clusters 1, 2, and 3). Two out of Five patient clusters (cluster 4 and 5) showed improvement in PROMIS GH-P scores that met a minimally clinically important difference at 1-year postoperative. CONCLUSIONS: The unsupervised ML algorithm identified patient clusters that had predictable changes in PROMs after TKA. It is a positive step toward providing precision medical care for each of our arthroplasty patients.

Structure-based protein and small molecule generation using EGNN and diffusion models: A comprehensive review.

Recent breakthroughs in deep learning have revolutionized protein sequence and structure prediction. These advancements are built on decades of protein design efforts, and are overcoming traditional time and cost limitations. Diffusion models, at the forefront of these innovations, significantly enhance design efficiency by automating knowledge acquisition. In the field of de novo protein design, the goal is to create entirely novel proteins with predetermined structures. Given the arbitrary positions of proteins in 3-D space, graph representations and their properties are widely used in protein generation studies. A critical requirement in protein modelling is maintaining spatial relationships under transformations (rotations, translations, and reflections). This property, known as equivariance, ensures that predicted protein characteristics adapt seamlessly to changes in orientation or position. Equivariant graph neural networks offer a solution to this challenge. By incorporating equivariant graph neural networks to learn the score of the probability density function in diffusion models, one can generate proteins with robust 3-D structural representations. This review examines the latest deep learning advancements, specifically focusing on frameworks that combine diffusion models with equivariant graph neural networks for protein generation.

Annealed fractional Lévy-Ito diffusion models for protein generation.

Protein generation has numerous applications in designing therapeutic antibodies and creating new drugs. Still, it is a demanding task due to the inherent complexities of protein structures and the limitations of current generative models. Proteins possess intricate geometry, and sampling their conformational space is challenging due to its high dimensionality. This paper introduces novel Markovian and non-Markovian generative diffusion models based on fractional stochastic differential equations and the Lévy distribution, allowing for a more effective exploration of the conformational space. The approach is applied to a dataset of 40,000 proteins and evaluated in terms of Fréchet distance, fidelity, and diversity, outperforming the state-of-the-art by 25.4%, 35.8%, and 11.8%, respectively.

ProtInteract: A deep learning framework for predicting protein-protein interactions.

Proteins mainly perform their functions by interacting with other proteins. Protein-protein interactions underpin various biological activities such as metabolic cycles, signal transduction, and immune response. However, due to the sheer number of proteins, experimental methods for finding interacting and non-interacting protein pairs are time-consuming and costly. We therefore developed the ProtInteract framework to predict protein-protein interaction. ProtInteract comprises two components: first, a novel autoencoder architecture that encodes each protein's primary structure to a lower-dimensional vector while preserving its underlying sequence attributes. This leads to faster training of the second network, a deep convolutional neural network (CNN) that receives encoded proteins and predicts their interaction under three different scenarios. In each scenario, the deep CNN predicts the class of a given encoded protein pair. Each class indicates different ranges of confidence scores corresponding to the probability of whether a predicted interaction occurs or not. The proposed framework features significantly low computational complexity and relatively fast response. The contributions of this work are twofold. First, ProtInteract assimilates the protein's primary structure into a pseudo-time series. Therefore, we leverage the nature of the time series of proteins and their physicochemical properties to encode a protein's amino acid sequence into a lower-dimensional vector space. This approach enables extracting highly informative sequence attributes while reducing computational complexity. Second, the ProtInteract framework utilises this information to identify protein interactions with other proteins based on its amino acid configuration. Our results suggest that the proposed framework performs with high accuracy and efficiency in predicting protein-protein interactions.

Protein-protein interaction prediction with deep learning: A comprehensive review.

Most proteins perform their biological function by interacting with themselves or other molecules. Thus, one may obtain biological insights into protein functions, disease prevalence, and therapy development by identifying protein-protein interactions (PPI). However, finding the interacting and non-interacting protein pairs through experimental approaches is labour-intensive and time-consuming, owing to the variety of proteins. Hence, protein-protein interaction and protein-ligand binding problems have drawn attention in the fields of bioinformatics and computer-aided drug discovery. Deep learning methods paved the way for scientists to predict the 3-D structure of proteins from genomes, predict the functions and attributes of a protein, and modify and design new proteins to provide desired functions. This review focuses on recent deep learning methods applied to problems including predicting protein functions, protein-protein interaction and their sites, protein-ligand binding, and protein design.