arXiv subjects

Andreas Bender

Publications and source records attributed to Andreas Bender.

At least 19 recordsLinked to original sources

arXiv2026

Automated sign detection across the Electronic Babylonian Library: A large-scale dataset and end-to-end cuneiform OCR pipeline

Learning to read cuneiform tablets is an extremely demanding task; consequently, of the roughly half million excavated tablets, only a small fraction has been analysed by Assyriologists. Computer vision offers a promising avenue for decipherment but requires large, densely annotated datasets. To address this limitation, the largest annotated cuneiform sign dataset to date is used, and a Deformable Detection Transformer (DETR)-based object detection model is evaluated under two class granularities of 173 and 106 classes. The proposed system integrates automatic tablet-side extraction, heuristic line grouping, and n-gram-based textual similarity evaluation to bridge visual sign detection and textual structure, and achieves consistent improvements of up to 28-37% over prior work on COCO-style detection metrics. At inference, the method is applied to 87,668 tablet fragments from the Electronic Babylonian Library (eBL) corpus, producing nearly 2.9 million sign detections. Although the approach operates without linguistic priors and remains sensitive to tablet damage and layout variability, it provides a scalable and interpretable foundation for corpus-wide cuneiform analysis and supports future integration with multimodal and linguistic modelling frameworks.

cs.CV↗

arXiv2026

Semantically Conditioned Diffusion Models for Cerebral DSA Synthesis

Digital subtraction angiography (DSA) plays a central role in the diagnosis and treatment of cerebrovascular disease, yet its invasive nature and high acquisition cost severely limit large-scale data collection and public data sharing. Therefore, we developed a semantically conditioned latent diffusion model (LDM) that synthesizes arterial-phase cerebral DSA frames under explicit control of anatomical circulation (anterior vs.\ posterior) and canonical C-arm positions. We curated a large single-centre DSA dataset of 99,349 frames and trained a conditional LDM using text embeddings that encoded anatomy and acquisition geometry. To assess clinical realism, four medical experts, including two neuroradiologists, one neurosurgeon, and one internal medicine expert, systematically rated 400 synthetic DSA images using a 5-grade Likert scale for evaluating proximal large, medium, and small peripheral vessels. The generated images achieved image-wise overall Likert scores ranging from 3.1 to 3.3, with high inter-rater reliability (ICC(2,k) = 0.80--0.87). Distributional similarity to real DSA frames was supported by a low median Fr\'echet inception distance (FID) of 15.27. Our results indicate that semantically controlled LDMs can produce realistic synthetic DSAs suitable for downstream algorithm development, research, and training.

cs.CV↗

arXiv2025

AI Agents in Drug Discovery

Artificial intelligence (AI) agents are emerging as transformative tools in drug discovery, with the ability to autonomously reason, act, and learn through complicated research workflows. Building on large language models (LLMs) coupled with perception, computation, action, and memory tools, these agentic AI systems could integrate diverse biomedical data, execute tasks, carry out experiments via robotic platforms, and iteratively refine hypotheses in closed loops. We provide a conceptual and technical overview of agentic AI architectures, ranging from ReAct and Reflection to Supervisor and Swarm systems, and illustrate their applications across key stages of drug discovery, including literature synthesis, toxicity prediction, automated protocol generation, small-molecule synthesis, drug repurposing, and end-to-end decision-making. To our knowledge, this represents the first comprehensive work to present real-world implementations and quantifiable impacts of agentic AI systems deployed in operational drug discovery settings. Early implementations demonstrate substantial gains in speed, reproducibility, and scalability, compressing workflows that once took months into hours while maintaining scientific traceability. We discuss the current challenges related to data heterogeneity, system reliability, privacy, and benchmarking, and outline future directions towards technology in support of science and translation.

cs.LG↗

arXiv2025

Multi-state Models For Disease Histories Based On Longitudinal Data

Multi-stage disease histories derived from longitudinal data are becoming increasingly available as registry data and biobanks expand. Multi-state models are suitable to investigate transitions between different disease stages in presence of competing risks. In this context, however, their estimation is complicated by dependent left-truncation, multiple time scales, index event bias, and interval-censoring. In this work, we investigate the extension of piecewise exponential additive models (PAMs) to this setting and their applicability given the above challenges. In simulation studies we show that PAMs can handle dependent left-truncation and accommodate multiple time scales. Compared to a stratified single time scale model, a multiple time scales model is found to be less robust to the data generating process. We also quantify the extent of index event bias in multiple settings, demonstrating its dependence on the completeness of covariate adjustment. In general, PAMs recover baseline and fixed effects well in most settings, except for baseline hazards in interval-censored data. Finally, we apply our framework to estimate multi-state transition hazards and probabilities of chronic kidney disease (CKD) onset and progression in a UK Biobank dataset (n=142,667). We observe CKD progression risk to be highest for individuals with early CKD onset and to further increase over age. In addition, the well-known genetic variant rs77924615 in the UMOD locus is found to be associated with CKD onset hazards, but not with risk of further CKD progression.

stat.ME↗

arXiv2025

Reduction Techniques for Survival Analysis

In this work, we discuss what we refer to as reduction techniques for survival analysis, that is, techniques that "reduce" a survival task to a more common regression or classification task, without ignoring the specifics of survival data. Such techniques particularly facilitate machine learning-based survival analysis, as they allow for applying standard tools from machine and deep learning to many survival tasks without requiring custom learners. We provide an overview of different reduction techniques and discuss their respective strengths and weaknesses. We also provide a principled implementation of some of these reductions, such that they are directly available within standard machine learning workflows. We illustrate each reduction using dedicated examples and perform a benchmark analysis that compares their predictive performance to established machine learning methods for survival analysis.

stat.ML↗

arXiv2025

Enhancing Traffic Accident Classifications: Application of NLP Methods for City Safety

A comprehensive understanding of traffic accidents is essential for improving city safety and informing policy decisions. In this study, we analyze traffic incidents in Munich to identify patterns and characteristics that distinguish different types of accidents. The dataset consists of both structured tabular features, such as location, time, and weather conditions, as well as unstructured free-text descriptions detailing the circumstances of each accident. Each incident is categorized into one of seven predefined classes. To assess the reliability of these labels, we apply NLP methods, including topic modeling and few-shot learning, which reveal inconsistencies in the labeling process. These findings highlight potential ambiguities in accident classification and motivate a refined predictive approach. Building on these insights, we develop a classification model that achieves high accuracy in assigning accidents to their respective categories. Our results demonstrate that textual descriptions contain the most informative features for classification, while the inclusion of tabular data provides only marginal improvements. These findings emphasize the critical role of free-text data in accident analysis and highlight the potential of transformer-based models in improving classification reliability.

cs.CL↗

arXiv2024

Benchmarking structure-based three-dimensional molecular generative models using GenBench3D: ligand conformation quality matters

Three-dimensional (3D) deep molecular generative models offer the advantage of goal-directed generation based on 3D-dependent properties, such as binding affinity for structure-based design within binding pockets. Traditional benchmarks created to evaluate SMILES or molecular graphs generators, such as GuacaMol or MOSES, are limited to evaluate 3D generators as they do not assess the quality of the generated molecular conformation. In this work, we hence developed GenBench3D, which implements a new benchmark for models producing molecules within a binding pocket. Our main contribution is the Validity3D metric, evaluating the conformation quality using the likelihood of bond lengths and valence angles based on reference values observed in the Cambridge Structural Database. The LiGAN, 3D-SBDD, Pocket2Mol, TargetDiff, DiffSBDD and ResGen models were benchmarked. We show that only between 0% and 11% of generated molecules have valid conformations. Performing local relaxation of generated molecules in the pocket considerably improved the Validity3D for all models by a minimum increase of 40%. For LiGAN, 3D-SBDD, or TargetDiff, the set of valid relaxed molecules shows on average higher Vina score (i.e. worse) than the set of raw generated molecules, indicating that the binding affinity of raw generated molecules might be overestimated. Using the other scoring functions, that give higher importance to ligand strain, only yield improved scores when using valid relaxed molecules. Using valid relaxed molecules, TargetDiff and Pocket2Mol show better median Vina, Glide and Gold PLP scores than other models. We have publicly released GenBench3D on GitHub for broader use: https://github.com/bbaillif/genbench3d

q-bio.QM↗

arXiv2024

A Large-Scale Neutral Comparison Study of Survival Models on Low-Dimensional Data

This work presents the first large-scale neutral benchmark experiment focused on single-event, right-censored, low-dimensional survival data. Benchmark experiments are essential in methodological research to scientifically compare new and existing model classes through proper empirical evaluation. Existing benchmarks in the survival literature are smaller in scale regarding the number of used datasets and extent of empirical evaluation. They often lack appropriate tuning or evaluation procedures, while other comparison studies focus on qualitative reviews rather than quantitative comparisons. This comprehensive study aims to fill the gap by neutrally evaluating a broad range of methods and providing generalizable guidelines for practitioners. We benchmark 19 models, ranging from classical statistical approaches to many common machine learning methods, on 34 publicly available datasets. The benchmark tunes models using both a discrimination measure (Harrell's C-index) and a scoring rule (Integrated Survival Brier Score), and evaluates them across six metrics covering discrimination, calibration, and overall predictive performance. Despite superior average ranks in overall predictive performance from individual learners like oblique random survival forests and likelihood-based boosting, and better discrimination rankings from multiple boosting- and tree-based methods as well as parametric survival models, no method significantly outperforms the commonly used Cox proportional hazards model for either tuning measure. We conclude that for predictive purposes in the standard survival analysis setting of low-dimensional, right-censored data, the Cox Proportional Hazards model remains a simple and robust method, sufficient for most practitioners. All code, data, and results are publicly available on GitHub https://github.com/slds-lmu/paper_2023_survival_benchmark

stat.ML↗

arXiv2024

A Decade in a Systematic Review: The Evolution and Impact of Cell Painting

High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology, mechanism of action, new therapeutics, and toxicology predictions. Here, we systematically review the substantial methodological advancements and applications of Cell Painting. Advancements include improvements in the Cell Painting protocol, assay adaptations for different types of perturbations and applications, and improved methodologies for feature extraction, quality control, and batch effect correction. Moreover, machine learning methods recently surpassed classical approaches in their ability to extract biologically useful information from Cell Painting images. Cell Painting data have been used alone or in combination with other -omics data to decipher the mechanism of action of a compound, its toxicity profile, and many other biological effects. Overall, key methodological advances have expanded the ability of Cell Painting to capture cellular responses to various perturbations. Future advances will likely lie in advancing computational and experimental techniques, developing new publicly available datasets, and integrating them with other high-content data types.

q-bio.SC↗

arXiv2024

On Training Survival Models with Scoring Rules

Scoring rules are an established way of comparing predictive performances across model classes. In the context of survival analysis, they require adaptation in order to accommodate censoring. This work investigates using scoring rules for model training rather than evaluation. Doing so, we establish a general framework for training survival models that is model agnostic and can learn event time distributions parametrically or non-parametrically. In addition, our framework is not restricted to any specific scoring rule. While we focus on neural network-based implementations, we also provide proof-of-concept implementations using gradient boosting, generalized additive models, and trees. Empirical comparisons on synthetic and real-world data indicate that scoring rules can be successfully incorporated into model training and yield competitive predictive performance with established time-to-event models.

cs.LG↗

arXiv2024

Understanding Biology in the Age of Artificial Intelligence

Modern life sciences research is increasingly relying on artificial intelligence approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet it is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research - protein structure prediction and single cell RNA-sequencing - we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems.

cs.AI↗

arXiv2023

Evaluating machine learning models in non-standard settings: An overview and new findings

Estimating the generalization error (GE) of machine learning models is fundamental, with resampling methods being the most common approach. However, in non-standard settings, particularly those where observations are not independently and identically distributed, resampling using simple random data divisions may lead to biased GE estimates. This paper strives to present well-grounded guidelines for GE estimation in various such non-standard settings: clustered data, spatial data, unequal sampling probabilities, concept drift, and hierarchically structured outcomes. Our overview combines well-established methodologies with other existing methods that, to our knowledge, have not been frequently considered in these particular settings. A unifying principle among these techniques is that the test data used in each iteration of the resampling procedure should reflect the new observations to which the model will be applied, while the training data should be representative of the entire data set used to obtain the final model. Beyond providing an overview, we address literature gaps by conducting simulation studies. These studies assess the necessity of using GE-estimation methods tailored to the respective setting. Our findings corroborate the concern that standard resampling methods often yield biased GE estimates in non-standard settings, underscoring the importance of tailored GE estimation.

stat.ML↗

arXiv2023

Deep Learning for Survival Analysis: A Review

The influx of deep learning (DL) techniques into the field of survival analysis in recent years has led to substantial methodological progress; for instance, learning from unstructured or high-dimensional data such as images, text or omics data. In this work, we conduct a comprehensive systematic review of DL-based methods for time-to-event analysis, characterizing them according to both survival- and DL-related attributes. In summary, the reviewed methods often address only a small subset of tasks relevant to time-to-event data - e.g., single-risk right-censored data - and neglect to incorporate more complex settings. Our findings are summarized in an editable, open-source, interactive table: https://survival-org.github.io/DL4Survival. As this research area is advancing rapidly, we encourage community contribution in order to keep this database up to date.

stat.ML↗

arXiv2022

When Are Scoring Rules Proper? Bridging Theory and Practice in Survival Model Evaluation

Proper scoring rules encourage probabilistic predictions that match the true underlying distribution and are central to model evaluation, with increasing relevance in automated workflows such as AutoML. In survival analysis, however, their behavior under censoring is not fully understood. We study commonly used squared and logarithmic scoring rules for right-censored survival data under independent censoring, introducing a notion of marginal properness based on observable outcomes. Within this framework, we show that the SBS, evaluated at a fixed time point, along with its integrated version (ISBS) and the RCLL are strictly proper when all individuals eventually experience the event, but can become improper under finite follow-up or in the presence of cure fractions. For the SBS, we derive a closed-form expression that reveals the true mechanism: residual mass, corresponding to individuals who remain event-free at study end, systematically biases the score toward underestimating survival, with the effect increasing at later evaluation times and under heavier censoring. Through simulation experiments, we examine how these issues manifest in finite samples and under misspecification. The SBS exhibits pronounced improperness at late evaluation times and poor discrimination between models. The ISBS is more robust due to temporal integration but remains sensitive to tail regularity violations, exhibiting detectable improperness and reduced discriminatory power. The RCLL behaves consistently with strict properness and effectively separates misspecified models. Overall, our results demonstrate how theoretical improperness can translate into misleading model comparisons, underscoring the need for further methodological development in survival model evaluation under censoring and realistic data conditions.

math.ST↗

arXiv2022

Re-evaluating sample efficiency in de novo molecule generation

De novo molecule generation can suffer from data inefficiency; requiring large amounts of training data or many sampled data points to conduct objective optimization. The latter is a particular disadvantage when combining deep generative models with computationally expensive molecule scoring functions (a.k.a. oracles) commonly used in computer-aided drug design. Recent works have therefore focused on methods to improve sample efficiency in the context of de novo molecule drug design, or to benchmark it. In this work, we discuss and adapt a recent sample efficiency benchmark to better reflect realistic goals also with respect to the quality of chemistry generated, which must always be considered in the context of small-molecule drug design; we then re-evaluate all benchmarked generative models. We find that accounting for molecular weight and LogP with respect to the training data, and the diversity of chemistry proposed, re-orders the ranking of generative models. In addition, we benchmark a recently proposed method to improve sample efficiency (Augmented Hill-Climb) and found it ranked top when considering both the sample efficiency and chemistry of molecules generated. Continual improvements in sample efficiency and chemical desirability enable more routine integration of computationally expensive scoring functions on a more realistic timescale.

cs.CE↗

arXiv2022

Conditional Neural Processes for Molecules

Neural processes (NPs) are models for transfer learning with properties reminiscent of Gaussian Processes (GPs). They are adept at modelling data consisting of few observations of many related functions on the same input space and are trained by minimizing a variational objective, which is computationally much less expensive than the Bayesian updating required by GPs. So far, most studies of NPs have focused on low-dimensional datasets which are not representative of realistic transfer learning tasks. Drug discovery is one application area that is characterized by datasets consisting of many chemical properties or functions which are sparsely observed, yet depend on shared features or representations of the molecular inputs. This paper applies the conditional neural process (CNP) to DOCKSTRING, a dataset of docking scores for benchmarking ML models. CNPs show competitive performance in few-shot learning tasks relative to supervised learning baselines common in chemoinformatics, as well as an alternative model for transfer learning based on pre-training and refining neural network regressors. We present a Bayesian optimization experiment which showcases the probabilistic nature of CNPs and discuss shortcomings of the model in uncertainty quantification.

stat.ML↗

arXiv2022

Heterogeneous Treatment Effect Estimation for Observational Data using Model-based Forests

The estimation of heterogeneous treatment effects (HTEs) has attracted considerable interest in many disciplines, most prominently in medicine and economics. Contemporary research has so far primarily focused on continuous and binary responses where HTEs are traditionally estimated by a linear model, which allows the estimation of constant or heterogeneous effects even under certain model misspecifications. More complex models for survival, count, or ordinal outcomes require stricter assumptions to reliably estimate the treatment effect. Most importantly, the noncollapsibility issue necessitates the joint estimation of treatment and prognostic effects. Model-based forests allow simultaneous estimation of covariate-dependent treatment and prognostic effects, but only for randomized trials. In this paper, we propose modifications to model-based forests to address the confounding issue in observational data. In particular, we evaluate an orthogonalization strategy originally proposed by Robinson (1988, Econometrica) in the context of model-based forests targeting HTE estimation in generalized linear models and transformation models. We found that this strategy reduces confounding effects in a simulated study with various outcome distributions. We demonstrate the practical aspects of HTE estimation for survival and ordinal outcomes by an assessment of the potentially heterogeneous effect of Riluzole on the progress of Amyotrophic Lateral Sclerosis.

stat.ME↗

arXiv2022

Factorized Structured Regression for Large-Scale Varying Coefficient Models

Recommender Systems (RS) pervade many aspects of our everyday digital life. Proposed to work at scale, state-of-the-art RS allow the modeling of thousands of interactions and facilitate highly individualized recommendations. Conceptually, many RS can be viewed as instances of statistical regression models that incorporate complex feature effects and potentially non-Gaussian outcomes. Such structured regression models, including time-aware varying coefficients models, are, however, limited in their applicability to categorical effects and inclusion of a large number of interactions. Here, we propose Factorized Structured Regression (FaStR) for scalable varying coefficient models. FaStR overcomes limitations of general regression models for large-scale data by combining structured additive regression and factorization approaches in a neural network-based model implementation. This fusion provides a scalable framework for the estimation of statistical models in previously infeasible data settings. Empirical results confirm that the estimation of varying coefficients of our approach is on par with state-of-the-art regression techniques, while scaling notably better and also being competitive with other time-aware RS in terms of prediction performance. We illustrate FaStR's performance and interpretability on a large-scale behavioral study with smartphone user data.

stat.ML↗