arXiv subjects

Ozan Öktem

Publications and source records attributed to Ozan Öktem.

At least 19 recordsLinked to original sources

arXiv2026

Recovering protein conformations from single-particle cryo-EM data via indirect shape matching gradient flows

Single-particle cryo-electron microscopy images a macromolecule as many noisy tomographic projections of its electrostatic potential. We reconstruct the protein backbone directly from such projections, as an atomic point cloud, without the intermediate step of reconstructing the 3D electrostatic potential map. We formulate this as an indirect shape matching problem: a point-cloud template of the backbone is deformed until its simulated projections agree with the data, with the structure observed only through the imaging operator. The deformation is computed via a gradient flow on a Lie group, and we derive the resulting framework in a general geometric setting before adapting it for single-particle cryo-electron microscopy. On synthetic data, we recover single- and multichain proteins and capture conformational transitions.

q-bio.BM↗

arXiv2026

Learned iterative networks: An operator learning perspective

Learned image reconstruction has become a pillar in computational imaging and inverse problems. Among the most successful approaches are learned iterative networks, which are formulated by unrolling classical iterative optimisation algorithms for solving variational problems. While the underlying algorithm is usually formulated in the functional analytic setting, learned approaches are often viewed as purely discrete. In this survey we present a unified operator view for learned iterative networks. Specifically, we formulate a learned reconstruction operator, defining how to compute, and separately the learning problem, which defines what to compute. In this setting we present common approaches and show that many approaches are closely related in their core. We review linear as well as non-linear inverse problems in this framework and present a short numerical study to conclude.

eess.IV↗

arXiv2026

Multiscale reconstruction of protein conformations from cryo-EM images

We present a novel multiscale algorithm for directly recovering the atomic model structure of a protein from single-particle cryo-EM data. Our algorithm is able to estimate protein structures to state-of-the-art accuracy for high-noise and low-contrast data. It is also robust to misspecifications in the TEM image formation model. These desirable properties are primarily due to the use of an explicit representation of the protein backbone in terms of bonds, torsion angles and bond angles, which supplies rich prior information to the structure recovery process. We apply our method on three protein cryo-EM datasets, generated using an electron microscope digital twin, and show that using a multiscale approach yields an improvement of the root-mean-square deviation (RMSD) and template modelling (TM) scores with respect to the ground truth. Furthermore, there is evidence that larger-scale structures are being prioritised with the multiscale algorithm, which reduces the possibility of convergence to bad local minima.

eess.IV↗

arXiv2026

Geometric shape matching for recovering protein conformations from single-particle Cryo-EM data

We address recovery of the three-dimensional backbone structure of single polypeptide proteins from single-particle cryo-electron microscopy (Cryo-SPA) data. Cryo-SPA produces noisy tomographic projections of electrostatic potentials of macromolecules. From these projections, we use methods from shape analysis to recover the three-dimensional backbone structure. Thus, we view the reconstruction problem as an indirect matching problem, where a point cloud representation of the protein backbone is deformed to match 2D tomography data. The deformations are obtained via the action of a matrix Lie group. By selecting a deformation energy, the optimality conditions are obtained, which lead to computational algorithms for optimal deformations. We showcase our approach on synthetic data, for which we recover the three-dimensional structure of the backbone.

q-bio.BM↗

arXiv2026

Motion-Enabled Tomography via Gaussian Mixture Models

Recovering physical properties of objects in motion is a core task across scientific and industrial applications. When the relative motion between the object and the sensing apparatus provides sufficient angular coverage, Computerized Tomography offers a powerful means of reconstruction. For such scenarios, we propose a parametric spatiotemporal model applied to Gaussian Mixture Models (GMM), in which each constituent Gaussian is parameterized by its own angular velocity, projectile motion, and geometry. GMM are a suitable means of reconstruction because they (i) admit accurate approximations in object space and (ii) have a closed form expression under the ray transform; enabling efficient forward predictions and exact gradient computations in data space. By decoupling the reconstruction problem into two sub-inverse problems, we characterize solutions as minimizers of task-specific objective functions that are derived and solved by utilizing the properties of (ii). The resulting algorithm we provide is applicable to objects in Euclidean space of arbitrary dimension. We validate the method on a simulated 2D problem, achieving accurate reconstruction of a 5-Gaussian GMM with intersecting trajectories. This also provides a foundation for further experimentation in settings with noisy data, 3D objects, and non-rigid body dynamics.

math.NA↗

arXiv2026

Protein Graph Neural Networks for Heterogeneous Cryo-EM Reconstruction

We present a geometry-aware method for heterogeneous single-particle cryogenic electron microscopy (cryo-EM) reconstruction that predicts atomic backbone conformations. To incorporate protein-structure priors, we represent the backbone as a graph and use a graph neural network (GNN) autodecoder that maps per-image latent variables to 3D displacements of a template conformation. The objective combines a data-discrepancy term based on a differentiable cryo-EM forward model with geometric regularization, and it supports unknown orientations via ellipsoidal support lifting (ESL) pose estimation. On synthetic datasets derived from molecular dynamics trajectories, the proposed GNN achieves higher accuracy compared to a multilayer perceptron (MLP) of comparable size, highlighting the benefits of a geometry-informed inductive bias.

cs.CV↗

arXiv2025

Improving the Generalisation of Learned Reconstruction Frameworks

Ensuring proper generalization is a critical challenge in applying data-driven methods for solving inverse problems in imaging, as neural networks reconstructing an image must perform well across varied datasets and acquisition geometries. In X-ray Computed Tomography (CT), convolutional neural networks (CNNs) are widely used to filter the projection data but are ill-suited for this task as they apply grid-based convolutions to the sinogram, which inherently lies on a line manifold, not a regular grid. The CNNs, unaware of the geometry, are implicitly tied to it and require an excessive amount of parameters as they must infer the relations between measurements from the data rather than from prior information. The contribution of this paper is twofold. First, we introduce a graph data structure to represent CT acquisition geometries and tomographic data, providing a detailed explanation of the graph's structure for circular, cone-beam geometries. Second, we propose GLM, a hybrid neural network architecture that leverages both graph and grid convolutions to process tomographic data. We demonstrate that GLM outperforms CNNs when performance is quantified in terms of structural similarity and peak signal-to-noise ratio, despite the fact that GLM uses only a fraction of the trainable parameters. Compared to CNNs, GLM also requires significantly less training time and memory, and its memory requirements scale better. Crucially, GLM demonstrates robust generalization to unseen variations in the acquisition geometry, like when training only on fully sampled CT data and then testing on sparse-view CT data.

eess.IV↗

arXiv2025

Sparse View Tomographic Reconstruction of Elongated Objects using Learned Primal-Dual Networks

In the wood industry, logs are commonly quality screened by discrete X-ray scans on a moving conveyor belt from a few source positions. Typically, the measurements are obtained in a single two-dimensional (2D) plane (a "slice") by a sequential scanning geometry. The data from each slice alone does not carry sufficient information for a three-dimensional tomographic reconstruction in which biological features of interest in the log are well preserved. In the present work, we propose a learned iterative reconstruction method based on the Learned Primal-Dual neural network, suited for sequential scanning geometries. Our method accumulates information between neighbouring slices, instead of only accounting for single slices during reconstruction. Evaluations were performed by training U-Nets on segmentation of knots (branches), which are crucial features in wood processing. Our quantitative and qualitative evaluations show that with as few as five source positions our method yields reconstructions of logs that are sufficiently accurate to identify biological features like knots (branches), heartwood and sapwood.

cs.AI↗

arXiv2025

Deep Micro Solvers for Rough-Wall Stokes Flow in a Heterogeneous Multiscale Method

We propose a learned precomputation for the heterogeneous multiscale method (HMM) for rough-wall Stokes flow. A Fourier neural operator is used to approximate local averages over microscopic subsets of the flow, which allows to compute an effective slip length of the fluid away from the roughness. The network is designed to map from the local wall geometry to the Riesz representors for the corresponding local flow averages. With such a parameterisation, the network only depends on the local wall geometry and as such can be trained independent of boundary conditions. We perform a detailed theoretical analysis of the statistical error propagation, and prove that under suitable regularity and scaling assumptions, a bounded training loss leads to a bounded error in the resulting macroscopic flow. We then demonstrate on a family of test problems that the learned precomputation performs stably with respect to the scale of the roughness. The accuracy in the HMM solution for the macroscopic flow is comparable to when the local (micro) problems are solved using a classical approach, while the computational cost of solving the micro problems is significantly reduced.

math.NA↗

arXiv2025

Pullback Flow Matching on Data Manifolds

We propose Pullback Flow Matching (PFM), a novel framework for generative modeling on data manifolds. Unlike existing methods that assume or learn restrictive closed-form manifold mappings for training Riemannian Flow Matching (RFM) models, PFM leverages pullback geometry and isometric learning to preserve the underlying manifold's geometry while enabling efficient generation and precise interpolation in latent space. This approach not only facilitates closed-form mappings on the data manifold but also allows for designable latent spaces, using assumed metrics on both data and latent manifolds. By enhancing isometric learning through Neural ODEs and proposing a scalable training objective, we achieve a latent space more suitable for interpolation, leading to improved manifold learning and generative performance. We demonstrate PFM's effectiveness through applications in synthetic data, protein dynamics and protein sequence data, generating novel proteins with specific properties. This method shows strong potential for drug discovery and materials science, where generating novel samples with specific properties is of great interest.

cs.LG↗

arXiv2025

Data-driven multi-agent modelling of calcium interactions in cell culture: PINN vs Regularized Least-squares

Data-driven discovery of dynamics in biological systems allows for better observation and characterization of processes, such as calcium signaling in cell culture. Recent advancements in techniques allow the exploration of previously unattainable insights of dynamical systems, such as the Sparse Identification of Non-Linear Dynamics (SINDy), overcoming the limitations of more classic methodologies. The latter requires some prior knowledge of an effective library of candidate terms, which is not realistic for a real case study. Using inspiration from fields like traffic density estimation and control theory, we propose a methodology for characterization and performance analysis of calcium delivery in a family of cells. In this work, we compare the performance of the Constrained Regularized Least-Squares Method (CRLSM) and Physics-Informed Neural Networks (PINN) for system identification and parameter discovery for governing ordinary differential equations (ODEs). The CRLSM achieves a fairly good parameter estimate and a good data fit when using the learned parameters in the Consensus problem. On the other hand, despite the initial hypothesis, PINNs fail to match the CRLSM performance and, under the current configuration, do not provide fair parameter estimation. However, we have only studied a limited number of PINN architectures, and it is expected that additional hyperparameter tuning, as well as uncertainty quantification, could significantly improve the performance in future works.

q-bio.QM↗

arXiv2024

Self-Supervised Denoiser Framework

Reconstructing images using Computed Tomography (CT) in an industrial context leads to specific challenges that differ from those encountered in other areas, such as clinical CT. Indeed, non-destructive testing with industrial CT will often involve scanning multiple similar objects while maintaining high throughput, requiring short scanning times, which is not a relevant concern in clinical CT. Under-sampling the tomographic data (sinograms) is a natural way to reduce the scanning time at the cost of image quality since the latter depends on the number of measurements. In such a scenario, post-processing techniques are required to compensate for the image artifacts induced by the sinogram sparsity. We introduce the Self-supervised Denoiser Framework (SDF), a self-supervised training method that leverages pre-training on highly sampled sinogram data to enhance the quality of images reconstructed from undersampled sinogram data. The main contribution of SDF is that it proposes to train an image denoiser in the sinogram space by setting the learning task as the prediction of one sinogram subset from another. As such, it does not require ground-truth image data, leverages the abundant data modality in CT, the sinogram, and can drastically enhance the quality of images reconstructed from a fraction of the measurements. We demonstrate that SDF produces better image quality, in terms of peak signal-to-noise ratio, than other analytical and self-supervised frameworks in both 2D fan-beam or 3D cone-beam CT settings. Moreover, we show that the enhancement provided by SDF carries over when fine-tuning the image denoiser on a few examples, making it a suitable pre-training technique in a context where there is little high-quality image data. Our results are established on experimental datasets, making SDF a strong candidate for being the building block of foundational image-enhancement models in CT.

eess.IV↗

arXiv2024

Neural incomplete factorization: learning preconditioners for the conjugate gradient method

The convergence of the conjugate gradient method for solving large-scale and sparse linear equation systems depends on the spectral properties of the system matrix, which can be improved by preconditioning. In this paper, we develop a computationally efficient data-driven approach to accelerate the generation of effective preconditioners. We, therefore, replace the typically hand-engineered preconditioners by the output of graph neural networks. Our method generates an incomplete factorization of the matrix and is, therefore, referred to as neural incomplete factorization (NeuralIF). Optimizing the condition number of the linear system directly is computationally infeasible. Instead, we utilize a stochastic approximation of the Frobenius loss which only requires matrix-vector multiplications for efficient training. At the core of our method is a novel message-passing block, inspired by sparse matrix theory, that aligns with the objective of finding a sparse factorization of the matrix. We evaluate our proposed method on both synthetic problem instances and on problems arising from the discretization of the Poisson equation on varying domains. Our experiments show that by using data-driven preconditioners within the conjugate gradient method we are able to speed up the convergence of the iterative procedure. The code is available at https://github.com/paulhausner/neural-incomplete-factorization.

math.OC↗

arXiv2024

Fast deep learning based reconstruction for limited angle tomography

A major challenge in computed tomography is reconstructing objects from incomplete data. An increasingly popular solution for these problems is to incorporate deep learning models into reconstruction algorithms. This study introduces a novel approach by integrating a Fourier neural operator (FNO) into the Filtered Backprojection (FBP) reconstruction method, yielding the FNO back projection (FNO-BP) network. We employ moment conditions for sinogram extrapolation to assist the model in mitigating artefacts from limited data. Notably, our deep learning architecture maintains a runtime comparable to classical filtered back projection (FBP) reconstructions, ensuring swift performance during both inference and training. We assess our reconstruction method in the context of the Helsinki Tomography Challenge 2022 and also compare it against regular FBP methods.

math.NA↗

arXiv2023

3D helical CT Reconstruction with a Memory Efficient Learned Primal-Dual Architecture

Deep learning based computed tomography (CT) reconstruction has demonstrated outstanding performance on simulated 2D low-dose CT data. This applies in particular to domain adapted neural networks, which incorporate a handcrafted physics model for CT imaging. Empirical evidence shows that employing such architectures reduces the demand for training data and improves upon generalisation. However, their training requires large computational resources that quickly become prohibitive in 3D helical CT, which is the most common acquisition geometry used for medical imaging. Furthermore, clinical data also comes with other challenges not accounted for in simulations, like errors in flux measurement, resolution mismatch and, most importantly, the absence of the real ground truth. The necessity to have a computationally feasible training combined with the need to address these issues has made it difficult to evaluate deep learning based reconstruction on clinical 3D helical CT. This paper modifies a domain adapted neural network architecture, the Learned Primal-Dual (LPD), so that it can be trained and applied to reconstruction in this setting. We achieve this by splitting the helical trajectory into sections and applying the unrolled LPD iterations to those sections sequentially. To the best of our knowledge, this work is the first to apply an unrolled deep learning architecture for reconstruction on full-sized clinical data, like those in the Low dose CT image and projection data set (LDCT). Moreover, training and testing is done on a single GPU card with 24GB of memory.

eess.IV↗

arXiv2023

Riemannian geometry for efficient analysis of protein dynamics data

An increasingly common viewpoint is that protein dynamics data sets reside in a non-linear subspace of low conformational energy. Ideal data analysis tools for such data sets should therefore account for such non-linear geometry. The Riemannian geometry setting can be suitable for a variety of reasons. First, it comes with a rich structure to account for a wide range of geometries that can be modelled after an energy landscape. Second, many standard data analysis tools initially developed for data in Euclidean space can also be generalised to data on a Riemannian manifold. In the context of protein dynamics, a conceptual challenge comes from the lack of a suitable smooth manifold and the lack of guidelines for constructing a smooth Riemannian structure based on an energy landscape. In addition, computational feasibility in computing geodesics and related mappings poses a major challenge. This work considers these challenges. The first part of the paper develops a novel local approximation technique for computing geodesics and related mappings on Riemannian manifolds in a computationally feasible manner. The second part constructs a smooth manifold of point clouds modulo rigid body group actions and a Riemannian structure that is based on an energy landscape for protein conformations. The resulting Riemannian geometry is tested on several data analysis tasks relevant for protein dynamics data. It performs exceptionally well on coarse-grained molecular dynamics simulated data. In particular, the geodesics with given start- and end-points approximately recover corresponding molecular dynamics trajectories for proteins that undergo relatively ordered transitions with medium sized deformations. The Riemannian protein geometry also gives physically realistic summary statistics and retrieves the underlying dimension even for large-sized deformations within seconds on a laptop.

q-bio.BM↗

arXiv2023

Regularising orientation estimation in Cryo-EM 3D map refinement through measure-based lifting over Riemannian manifolds

Motivated by the trade-off between noise-robustness and data-consistency for joint 3D map reconstruction and rotation estimation in single particle cryogenic-electron microscopy (Cryo-EM), we propose ellipsoidal support lifting (ESL), a measure-based lifting scheme for regularising and approximating the global minimiser of a smooth function over a Riemannian manifold. Under a uniqueness assumption on the minimiser we show several theoretical results, in particular well-posedness of the method and an error bound due to the induced bias with respect to the global minimiser. Additionally, we use the developed theory to integrate the measure-based lifting scheme into an alternating update method for joint homogeneous 3D map reconstruction and rotation estimation, where typically tens of thousands of manifold-valued minimisation problems have to be solved and where regularisation is necessary because of the high noise levels in the data. The joint recovery method is used to test both the theoretical predictions and algorithmic performance through numerical experiments with Cryo-EM data. In particular, the induced bias due to the regularising effect of ESL empirically estimates better rotations, i.e., rotations closer to the ground truth, than global optimisation would.

math.OC↗

arXiv2022

Spectral decomposition of atomic structures in heterogeneous cryo-EM

We consider the problem of recovering the three-dimensional atomic structure of a flexible macromolecule from a heterogeneous cryo-EM dataset. The dataset contains noisy tomographic projections of the electrostatic potential of the macromolecule, taken from different viewing directions, and in the heterogeneous case, each image corresponds to a different conformation of the macromolecule. Under the assumption that the macromolecule can be modelled as a chain, or discrete curve (as it is for instance the case for a protein backbone with a single chain of amino-acids), we introduce a method to estimate the deformation of the atomic model with respect to a given conformation, which is assumed to be known a priori. Our method consists on estimating the torsion and bond angles of the atomic model in each conformation as a linear combination of the eigenfunctions of the Laplace operator in the manifold of conformations. These eigenfunctions can be approximated by means of a well-known technique in manifold learning, based on the construction of a graph Laplacian using the cryo-EM dataset. Finally, we test our approach with synthetic datasets, for which we recover the atomic model of two-dimensional and three-dimensional flexible structures from noisy tomographic projections.

eess.IV↗