Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based therapeutics and materials. Structure-based protein design aims to find structures that are designable (can be realized by a protein sequence), novel (have dissimilar geometry from natural proteins), and diverse (span a wide range of geometries). While advances in protein structure prediction have made it possible to predict structures of novel protein sequences, the combinatorially large space of sequences and structures limits the practicality of search-based methods. Generative models provide a compelling alternative, by implicitly learning the low-dimensional structure of complex data distributions. Here, we leverage recent advances in denoising diffusion probabilistic models and equivariant neural networks to develop Genie, a generative model of protein structures that performs discrete-time diffusion using a cloud of oriented reference frames in 3D space. Through in silico evaluations, we demonstrate that Genie generates protein backbones that are more designable, novel, and diverse than existing models. This indicates that Genie is capturing key aspects of the distribution of protein structure space and facilitates protein design with high success rates. Code for generating new proteins and training new versions of Genie is available at https://github.com/aqlaboratory/genie.

In predictive tasks, real-world datasets often present different degrees of imbalanced (i.e., long-tailed or skewed) distributions. While the majority (the head) classes have sufficient samples, the minority (the tail) classes can be under-represented by a rather limited number of samples. Data pre-processing has been shown to be very effective in dealing with such problems. On one hand, data re-sampling is a common approach to tackling class imbalance. On the other hand, dimension reduction, which reduces the feature space, is a conventional technique for reducing noise and inconsistencies in a dataset. However, the possible synergy between feature selection and data re-sampling for high-performance imbalance classification has rarely been investigated before. To address this issue, we carry out a comprehensive empirical study on the joint influence of feature selection and re-sampling on two-class imbalance classification. Specifically, we study the performance of two opposite pipelines for imbalance classification by applying feature selection before or after data re-sampling. We conduct a large number of experiments, with a total of 9225 tests, on 52 publicly available datasets, using 9 feature selection methods, 6 re-sampling approaches for class imbalance learning, and 3 well-known classification algorithms. Experimental results show that there is no constant winner between the two pipelines; thus both of them should be considered to derive the best performing model for imbalance classification. We find that the performance of an imbalance classification model not only depends on the classifier adopted and the ratio between the number of majority and minority samples, but also depends on the ratio between the number of samples and features. Overall, this study should provide new reference value for researchers and practitioners in imbalance learning.

The goal of supervised Machine Learning is to build a prediction function based on historical data. This data has independent (explanatory) variables and a target variable (the variable that you want to predict). Once a predictive model has been built, we measure its error on a separate testing data set. We do this using KPIs that allow quantifying the error of the model, for example, the Mean Square Error in a regression context (quantitative target variable) or the Accuracy in a classification context (categorical target variable). The model with the smallest error is generally selected as the best model.