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Christoph Lippert

Publications and source records attributed to Christoph Lippert.

At least 19 recordsLinked to original sources

Localizing predictive concepts encoded in neural representations via hierarchical testing

Understanding which regulatory sequence motifs a genomic deep learning model has learned, with statistical error guarantees, is essential for trusting its use in downstream tasks such as variant effect prediction. Existing approaches to identifying which units in a trained network encode human- understandable concepts fall into two groups. Exploratory methods rank and visualize units but offer no statistical guarantee that the selected units are associated with the prediction target across the population of inputs. Testing-based methods test only single units or one pre-defined set of them, and do not control the error across the many sets of units. We introduce CUTTIE (Cluster-tree Unit Top-down Testing of Independence with Error control), which clusters the units of each layer into a tree and tests the clusters top-down with conditional independence tests, localizing information about the target while controlling the family-wise error rate. Thereby, we identify clusters that carry information about the target beyond the rest of the layer. For the units in the identified clusters, conditional attribution maps then reveal what motifs they encode. In a controlled simulation, the procedure identifies the clusters whose concepts affect the target. We apply the procedure to a convolutional model predicting cell-type-specific chromatin accessibility from DNA sequence, where the concepts encoded in the identified clusters map onto known regulatory motifs.

cs.LG↗

Two-Sample Testing via Path-based Inference

Modern deep generative models are primarily studied for their ability to generate realistic samples, yet the generative dynamics they learn can also serve as objects of statistical inference. We develop this idea for two-sample testing, the problem of deciding whether the same distribution generated two finite datasets. Using stochastic interpolants, we connect both distributions to a shared Gaussian bottleneck, so that each half of the resulting path is a Gaussian channel acting on a single population. We prove that the null hypothesis holds if and only if the population denoiser, or equivalently, the velocity fields of the two halves, coincide at any single noise level, which amounts to a reflection symmetry of the path about the bottleneck. Deviations from this symmetry yield a continuum of two-sample witnesses, which we estimate via held-out regression risks on learned denoisers and velocities and aggregate along the path; under an information-theoretic weighting, the aggregated discrepancy equals the Jeffreys divergence between the noise-smoothed distributions. Calibrating the resulting statistics by permutation yields tests that are valid in finite samples for any trained networks and consistent when the fields are learned accurately. On a synthetic benchmark and three image benchmarks, the proposed tests improve power over the strongest baseline by up to 33 percentage points at an equal total sample budget, with the best choice of regression representation and path weighting depending on the data modality. These results show that generative paths provide a principled representation for statistical testing, extending stochastic-interpolant models beyond generation.

stat.ML↗

CORTEX: A Structured Reasoning Benchmark for Trustworthy 3D Chest CT MLLMs

Reasoning in multimodal large language models (MLLMs) has shown strong promise in medical imaging. However, this reasoning is usually free-form text judged only by its final answer, making it hard to interpret and verify, especially in 3D radiology, where a diagnosis should be traceable to evidence in the scan. Existing chest CT question-answering datasets compound this by reducing expert radiology reports to answer-only pairs, dropping the reasoning that links findings to conclusions and omitting the patient history clinicians rely on. As a result, reasoning-capable 3D chest CT MLLMs remain out of reach, as neither the structured supervision needed to train them nor the protocol needed to verify their reasoning yet exists. We introduce CORTEX (Clinically Organized Reasoning and sTructured EXplanation), a structured reasoning benchmark for 3D chest CT. For each question, CORTEX restores the missing reasoning as a four-stage diagnostic trace mirroring a radiologist's workflow: task understanding, visual observation, diagnostic reasoning, and answer synthesis. We generate these traces using frontier large language models with broad medical and general-domain knowledge, then filter and verify them with a stage-level evaluation protocol combining automated rubric scoring with expert radiologist review. Crucially, both the reasoning structure and evaluation rubrics are designed in close collaboration with clinicians. Built on CT-RATE, a large, publicly available chest CT dataset without reasoning annotations, CORTEX comprises 76,177 validated reasoning traces across open-ended VQA, closed-ended VQA, and report generation, providing both the structured supervision and the stage-level evaluation protocol needed to build and evaluate trustworthy reasoning models for 3D chest CT. Our dataset and evaluation code is available at https://huggingface.co/datasets/aneesurhashmi/cortex

cs.CV↗

Embedded Conditional Independence Tests for Large Language Model Generated Text with an Application to German Parliament Speeches

Conditional independence tests (CITs) test for conditional dependence between two random objects $X$ and $Y$ given a third random object $Z$. Existing CITs have limited applicability to high-dimensional data, especially multimodal data like text. However, we show that such tests are of interest for large language model (LLM) outputs, where we test whether an output $X$ generated from a source text $Z$ carries information about an attribute $Y$ beyond $Z$ itself. For this purpose, we propose embedded CITs (eCITs), which embed $X$ and $Z$ and apply an existing CIT to the resulting representations and to $Y$. We show that, provided the embedding of $Z$ is sufficient, i.e. retains the information $Z$ carries about either $Y$ or the representation of $X$, the null hypothesis transfers from $X$ and $Z$ to their representations, so that a CIT valid for the embedded hypothesis is valid for the original one. We further give conditions for equivalence of the two hypotheses, and show that sufficiency weakens to mean sufficiency when the embedded test targets conditional mean independence. We propose a semi-synthetic simulation design to assess type I error (T1E) control and power of the eCITs for given embedding maps on a specific dataset and task, and use it to evaluate them on our application. Applying the eCITs to German Parliament speeches, we find for all combinations of embedding maps considered that the summaries of two LLMs contain information about the speaker's faction and gender beyond the speech they were generated from.

stat.ML↗

Counterfactual Explanations for Deep Two-Sample Testing

Two-sample testing is a fundamental tool for detecting distributional differences across scientific domains, but classical tests (including kernel-based tests) can be ineffective on high-dimensional structured data such as images. Recent deep two-sample tests improve sensitivity in these settings by learning informative representations, yet they provide limited insight into which data features drive rejection of the null hypothesis $H_0$. To address this issue, we propose a counterfactual explanation framework for deep two-sample testing that generates sample-level edits moving observations from a source group toward a target group while explicitly reducing the discrepancy measured by the test. Our method combines a diffusion autoencoder with a pretrained deep two-sample test model and optimizes a maximum mean discrepancy (MMD) objective in the test model's representation space to produce plausible counterfactuals. We quantify distribution-level effects through changes in the test statistic and the resulting two-sample p-values. We evaluate the method on synthetic 2D shape datasets and two MRI cohorts. Across both settings, the counterfactual transformations consistently increase p-values relative to the original samples, indicating that the edited source set becomes statistically closer to the target distribution under the test. We measure minimality using LPIPS to ensure the counterfactuals remain close to the original samples. The resulting edits provide interpretable evidence of the features associated with the detected group differences. On MRI, the localized changes are consistent with known anatomical differences between cohorts.

stat.ML↗

AnatomiX, an Anatomy-Aware Grounded Multimodal Large Language Model for Chest X-Ray Interpretation

Multimodal medical large language models have shown substantial progress in chest X-ray interpretation but continue to face challenges in spatial reasoning and anatomical understanding. Although existing grounding techniques improve overall performance, they often fail to establish a true anatomical correspondence, resulting in incorrect anatomical understanding in the medical domain. To address this gap, we introduce AnatomiX, a multitask multimodal large language model for anatomically grounded chest X-ray interpretation. Inspired by the radiological workflow, AnatomiX adopts a two stage approach: first, it identifies anatomical structures and extracts their features, and then leverages a large language model to perform diverse downstream tasks such as phrase grounding, report generation, visual question answering, and image understanding. Extensive experiments across multiple benchmarks demonstrate that AnatomiX achieves superior anatomical reasoning and delivers over 25% improvement in performance on anatomy grounding, phrase grounding, grounded diagnosis and grounded captioning tasks compared to existing approaches. Code and pretrained model are available at https://aneesurhashmi.github.io/anatomix

cs.CV↗

Towards Visually Explaining Statistical Tests with Applications in Biomedical Imaging

Deep neural two-sample tests have recently shown strong power for detecting distributional differences between groups, yet their black-box nature limits interpretability and practical adoption in biomedical analysis. Moreover, most existing post-hoc explainability methods rely on class labels, making them unsuitable for label-free statistical testing settings. We propose an explainable deep statistical testing framework that augments deep two-sample tests with sample-level and feature-level explanations, revealing which individual samples and which input features drive statistically significant group differences. Our method highlights which image regions and which individual samples contribute most to the detected group difference, providing spatial and instance-wise insight into the test's decision. Applied to biomedical imaging data, the proposed framework identifies influential samples and highlights anatomically meaningful regions associated with disease-related variation. This work bridges statistical inference and explainable AI, enabling interpretable, label-free population analysis in medical imaging.

cs.CV↗

On the Challenges and Opportunities in Generative AI

The field of deep generative modeling has grown rapidly in the last few years. With the availability of massive amounts of training data coupled with advances in scalable unsupervised learning paradigms, recent large-scale generative models show tremendous promise in synthesizing high-resolution images and text, as well as structured data such as videos and molecules. However, we argue that current large-scale generative AI models exhibit several fundamental shortcomings that hinder their widespread adoption across domains. In this work, our objective is to identify these issues and highlight key unresolved challenges in modern generative AI paradigms that should be addressed to further enhance their capabilities, versatility, and reliability. By identifying these challenges, we aim to provide researchers with insights for exploring fruitful research directions, thus fostering the development of more robust and accessible generative AI solutions.

cs.LG↗

JANET: Joint Adaptive predictioN-region Estimation for Time-series

Conformal prediction provides machine learning models with prediction sets that offer theoretical guarantees, but the underlying assumption of exchangeability limits its applicability to time series data. Furthermore, existing approaches struggle to handle multi-step ahead prediction tasks, where uncertainty estimates across multiple future time points are crucial. We propose JANET (Joint Adaptive predictioN-region Estimation for Time-series), a novel framework for constructing conformal prediction regions that are valid for both univariate and multivariate time series. JANET generalises the inductive conformal framework and efficiently produces joint prediction regions with controlled K-familywise error rates, enabling flexible adaptation to specific application needs. Our empirical evaluation demonstrates JANET's superior performance in multi-step prediction tasks across diverse time series datasets, highlighting its potential for reliable and interpretable uncertainty quantification in sequential data.

stat.ML↗

JAPAN: Joint Adaptive Prediction Areas with Normalising-Flows

Conformal prediction provides a model-agnostic framework for uncertainty quantification with finite-sample validity guarantees, making it an attractive tool for constructing reliable prediction sets. However, existing approaches commonly rely on residual-based conformity scores, which impose geometric constraints and struggle when the underlying distribution is multimodal. In particular, they tend to produce overly conservative prediction areas centred around the mean, often failing to capture the true shape of complex predictive distributions. In this work, we introduce JAPAN (Joint Adaptive Prediction Areas with Normalising-Flows), a conformal prediction framework that uses density-based conformity scores. By leveraging flow-based models, JAPAN estimates the (predictive) density and constructs prediction areas by thresholding on the estimated density scores, enabling compact, potentially disjoint, and context-adaptive regions that retain finite-sample coverage guarantees. We theoretically motivate the efficiency of JAPAN and empirically validate it across multivariate regression and forecasting tasks, demonstrating good calibration and tighter prediction areas compared to existing baselines. We also provide several \emph{extensions} adding flexibility to our proposed framework.

stat.ML↗

Automated Demand Forecasting in small to medium-sized enterprises

In response to the growing demand for accurate demand forecasts, this research proposes a generalized automated sales forecasting pipeline tailored for small- to medium-sized enterprises (SMEs). Unlike large corporations with dedicated data scientists for sales forecasting, SMEs often lack such resources. To address this, we developed a comprehensive forecasting pipeline that automates time series sales forecasting, encompassing data preparation, model training, and selection based on validation results. The development included two main components: model preselection and the forecasting pipeline. In the first phase, state-of-the-art methods were evaluated on a showcase dataset, leading to the selection of ARIMA, SARIMAX, Holt-Winters Exponential Smoothing, Regression Tree, Dilated Convolutional Neural Networks, and Generalized Additive Models. An ensemble prediction of these models was also included. Long-Short-Term Memory (LSTM) networks were excluded due to suboptimal prediction accuracy, and Facebook Prophet was omitted for compatibility reasons. In the second phase, the proposed forecasting pipeline was tested with SMEs in the food and electric industries, revealing variable model performance across different companies. While one project-based company derived no benefit, others achieved superior forecasts compared to naive estimators. Our findings suggest that no single model is universally superior. Instead, a diverse set of models, when integrated within an automated validation framework, can significantly enhance forecasting accuracy for SMEs. These results emphasize the importance of model diversity and automated validation in addressing the unique needs of each business. This research contributes to the field by providing SMEs access to state-of-the-art sales forecasting tools, enabling data-driven decision-making and improving operational efficiency.

econ.EM↗

Token Cropr: Faster ViTs for Quite a Few Tasks

The adoption of Vision Transformers (ViTs) in resource-constrained applications necessitates improvements in inference throughput. To this end several token pruning and merging approaches have been proposed that improve efficiency by successively reducing the number of tokens. However, it remains an open problem to design a token reduction method that is fast, maintains high performance, and is applicable to various vision tasks. In this work, we present a token pruner that uses auxiliary prediction heads that learn to select tokens end-to-end based on task relevance. These auxiliary heads can be removed after training, leading to throughput close to that of a random pruner. We evaluate our method on image classification, semantic segmentation, object detection, and instance segmentation, and show speedups of 1.5 to 4x with small drops in performance. As a best case, on the ADE20k semantic segmentation benchmark, we observe a 2x speedup relative to the no-pruning baseline, with a negligible performance penalty of 0.1 median mIoU across 5 seeds.

cs.CV↗

Conformalised Conditional Normalising Flows for Joint Prediction Regions in time series

Conformal Prediction offers a powerful framework for quantifying uncertainty in machine learning models, enabling the construction of prediction sets with finite-sample validity guarantees. While easily adaptable to non-probabilistic models, applying conformal prediction to probabilistic generative models, such as Normalising Flows is not straightforward. This work proposes a novel method to conformalise conditional normalising flows, specifically addressing the problem of obtaining prediction regions for multi-step time series forecasting. Our approach leverages the flexibility of normalising flows to generate potentially disjoint prediction regions, leading to improved predictive efficiency in the presence of potential multimodal predictive distributions.

stat.ML↗

Deep Nonparametric Conditional Independence Tests for Images

Conditional independence tests (CITs) test for conditional dependence between random variables. As existing CITs are limited in their applicability to complex, high-dimensional variables such as images, we introduce deep nonparametric CITs (DNCITs). The DNCITs combine embedding maps, which extract feature representations of high-dimensional variables, with nonparametric CITs applicable to these feature representations. For the embedding maps, we derive general properties on their parameter estimators to obtain valid DNCITs and show that these properties include embedding maps learned through (conditional) unsupervised or transfer learning. For the nonparametric CITs, appropriate tests are selected and adapted to be applicable to feature representations. Through simulations, we investigate the performance of the DNCITs for different embedding maps and nonparametric CITs under varying confounder dimensions and confounder relationships. We apply the DNCITs to brain MRI scans and behavioral traits, given confounders, of healthy individuals from the UK Biobank (UKB), confirming null results from a number of ambiguous personality neuroscience studies with a larger data set and with our more powerful tests. In addition, in a confounder control study, we apply the DNCITs to brain MRI scans and a confounder set to test for sufficient confounder control, leading to a potential reduction in the confounder dimension under improved confounder control compared to existing state-of-the-art confounder control studies for the UKB. Finally, we provide an R package implementing the DNCITs.

stat.ML↗

Kernelised Normalising Flows

Normalising Flows are non-parametric statistical models characterised by their dual capabilities of density estimation and generation. This duality requires an inherently invertible architecture. However, the requirement of invertibility imposes constraints on their expressiveness, necessitating a large number of parameters and innovative architectural designs to achieve good results. Whilst flow-based models predominantly rely on neural-network-based transformations for expressive designs, alternative transformation methods have received limited attention. In this work, we present Ferumal flow, a novel kernelised normalising flow paradigm that integrates kernels into the framework. Our results demonstrate that a kernelised flow can yield competitive or superior results compared to neural network-based flows whilst maintaining parameter efficiency. Kernelised flows excel especially in the low-data regime, enabling flexible non-parametric density estimation in applications with sparse data availability.

stat.ML↗

MixerFlow: MLP-Mixer meets Normalising Flows

Normalising flows are generative models that transform a complex density into a simpler density through the use of bijective transformations enabling both density estimation and data generation from a single model. %However, the requirement for bijectivity imposes the use of specialised architectures. In the context of image modelling, the predominant choice has been the Glow-based architecture, whereas alternative architectures remain largely unexplored in the research community. In this work, we propose a novel architecture called MixerFlow, based on the MLP-Mixer architecture, further unifying the generative and discriminative modelling architectures. MixerFlow offers an efficient mechanism for weight sharing for flow-based models. Our results demonstrate comparative or superior density estimation on image datasets and good scaling as the image resolution increases, making MixerFlow a simple yet powerful alternative to the Glow-based architectures. We also show that MixerFlow provides more informative embeddings than Glow-based architectures and can integrate many structured transformations such as splines or Kolmogorov-Arnold Networks.

stat.ML↗

Metadata-guided Feature Disentanglement for Functional Genomics

With the development of high-throughput technologies, genomics datasets rapidly grow in size, including functional genomics data. This has allowed the training of large Deep Learning (DL) models to predict epigenetic readouts, such as protein binding or histone modifications, from genome sequences. However, large dataset sizes come at a price of data consistency, often aggregating results from a large number of studies, conducted under varying experimental conditions. While data from large-scale consortia are useful as they allow studying the effects of different biological conditions, they can also contain unwanted biases from confounding experimental factors. Here, we introduce Metadata-guided Feature Disentanglement (MFD) - an approach that allows disentangling biologically relevant features from potential technical biases. MFD incorporates target metadata into model training, by conditioning weights of the model output layer on different experimental factors. It then separates the factors into disjoint groups and enforces independence of the corresponding feature subspaces with an adversarially learned penalty. We show that the metadata-driven disentanglement approach allows for better model introspection, by connecting latent features to experimental factors, without compromising, or even improving performance in downstream tasks, such as enhancer prediction, or genetic variant discovery. The code for our implemementation is available at https://github.com/HealthML/MFD

q-bio.GN↗

Interpretable and Interactive Deep Multiple Instance Learning for Dental Caries Classification in Bitewing X-rays

We propose a simple and efficient image classification architecture based on deep multiple instance learning, and apply it to the challenging task of caries detection in dental radiographs. Technically, our approach contributes in two ways: First, it outputs a heatmap of local patch classification probabilities despite being trained with weak image-level labels. Second, it is amenable to learning from segmentation labels to guide training. In contrast to existing methods, the human user can faithfully interpret predictions and interact with the model to decide which regions to attend to. Experiments are conducted on a large clinical dataset of $\sim$38k bitewings ($\sim$316k teeth), where we achieve competitive performance compared to various baselines. When guided by an external caries segmentation model, a significant improvement in classification and localization performance is observed.

eess.IV↗