arXiv subjects

Thomas Frerix

Publications and source records attributed to Thomas Frerix.

6 recordsLinked to original sources

arXiv2024

De novo design of high-affinity protein binders with AlphaProteo

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity binders without multiple rounds of experimental testing remains an unsolved challenge. This technical report introduces AlphaProteo, a family of machine learning models for protein design, and details its performance on the de novo binder design problem. With AlphaProteo, we achieve 3- to 300-fold better binding affinities and higher experimental success rates than the best existing methods on seven target proteins. Our results suggest that AlphaProteo can generate binders "ready-to-use" for many research applications using only one round of medium-throughput screening and no further optimization.

q-bio.BM↗

arXiv2021

Variational Data Assimilation with a Learned Inverse Observation Operator

Variational data assimilation optimizes for an initial state of a dynamical system such that its evolution fits observational data. The physical model can subsequently be evolved into the future to make predictions. This principle is a cornerstone of large scale forecasting applications such as numerical weather prediction. As such, it is implemented in current operational systems of weather forecasting agencies across the globe. However, finding a good initial state poses a difficult optimization problem in part due to the non-invertible relationship between physical states and their corresponding observations. We learn a mapping from observational data to physical states and show how it can be used to improve optimizability. We employ this mapping in two ways: to better initialize the non-convex optimization problem, and to reformulate the objective function in better behaved physics space instead of observation space. Our experimental results for the Lorenz96 model and a two-dimensional turbulent fluid flow demonstrate that this procedure significantly improves forecast quality for chaotic systems.

cs.LG↗

arXiv2019

Approximating Orthogonal Matrices with Effective Givens Factorization

We analyze effective approximation of unitary matrices. In our formulation, a unitary matrix is represented as a product of rotations in two-dimensional subspaces, so-called Givens rotations. Instead of the quadratic dimension dependence when applying a dense matrix, applying such an approximation scales with the number factors, each of which can be implemented efficiently. Consequently, in settings where an approximation is once computed and then applied many times, such a representation becomes advantageous. Although effective Givens factorization is not possible for generic unitary operators, we show that minimizing a sparsity-inducing objective with a coordinate descent algorithm on the unitary group yields good factorizations for structured matrices. Canonical applications of such a setup are orthogonal basis transforms. We demonstrate numerical results of approximating the graph Fourier transform, which is the matrix obtained when diagonalizing a graph Laplacian.

math.OC↗

arXiv2019

Homogeneous Linear Inequality Constraints for Neural Network Activations

We propose a method to impose homogeneous linear inequality constraints of the form $Ax\leq 0$ on neural network activations. The proposed method allows a data-driven training approach to be combined with modeling prior knowledge about the task. One way to achieve this task is by means of a projection step at test time after unconstrained training. However, this is an expensive operation. By directly incorporating the constraints into the architecture, we can significantly speed-up inference at test time; for instance, our experiments show a speed-up of up to two orders of magnitude over a projection method. Our algorithm computes a suitable parameterization of the feasible set at initialization and uses standard variants of stochastic gradient descent to find solutions to the constrained network. Thus, the modeling constraints are always satisfied during training. Crucially, our approach avoids to solve an optimization problem at each training step or to manually trade-off data and constraint fidelity with additional hyperparameters. We consider constrained generative modeling as an important application domain and experimentally demonstrate the proposed method by constraining a variational autoencoder.

cs.LG↗

arXiv2017

Associative Domain Adaptation

We propose associative domain adaptation, a novel technique for end-to-end domain adaptation with neural networks, the task of inferring class labels for an unlabeled target domain based on the statistical properties of a labeled source domain. Our training scheme follows the paradigm that in order to effectively derive class labels for the target domain, a network should produce statistically domain invariant embeddings, while minimizing the classification error on the labeled source domain. We accomplish this by reinforcing associations between source and target data directly in embedding space. Our method can easily be added to any existing classification network with no structural and almost no computational overhead. We demonstrate the effectiveness of our approach on various benchmarks and achieve state-of-the-art results across the board with a generic convolutional neural network architecture not specifically tuned to the respective tasks. Finally, we show that the proposed association loss produces embeddings that are more effective for domain adaptation compared to methods employing maximum mean discrepancy as a similarity measure in embedding space.

cs.CV↗

arXiv2017

Proximal Backpropagation

We propose proximal backpropagation (ProxProp) as a novel algorithm that takes implicit instead of explicit gradient steps to update the network parameters during neural network training. Our algorithm is motivated by the step size limitation of explicit gradient descent, which poses an impediment for optimization. ProxProp is developed from a general point of view on the backpropagation algorithm, currently the most common technique to train neural networks via stochastic gradient descent and variants thereof. Specifically, we show that backpropagation of a prediction error is equivalent to sequential gradient descent steps on a quadratic penalty energy, which comprises the network activations as variables of the optimization. We further analyze theoretical properties of ProxProp and in particular prove that the algorithm yields a descent direction in parameter space and can therefore be combined with a wide variety of convergent algorithms. Finally, we devise an efficient numerical implementation that integrates well with popular deep learning frameworks. We conclude by demonstrating promising numerical results and show that ProxProp can be effectively combined with common first order optimizers such as Adam.

cs.LG↗