arXiv subjects

Uwe Ohler

Publications and source records attributed to Uwe Ohler.

6 recordsLinked to original sources

arXiv2026

Uncertainty-Aware Deep Learning for Genomics Applications: Insights from an Empirical Study

Deep learning models have emerged as the standard computational tool for a wide range of applications in genomics. Yet, uncertainty quantification (UQ) --- and more specifically, the reliability of different uncertainty estimates in this domain --- has received little systematic attention. This work presents an empirical analysis of UQ in deep learning models, focusing on genomics applications. In a series of experiments, we contrast Deep Ensembles, Bayesian Neural Networks, and Monte Carlo-dropout methods. We assess their ability to quantify uncertainty in different scenarios, accounting for common dataset characteristics in two genomic application areas and modalities: sequence-to-activity models and single-cell expression analysis. Our systematic comparison framework provides guidelines for the applicability and reliability of UQ methods in genomics, highlighting their strengths and limitations in different scenarios. Our results indicate that Bayesian Neural Networks give the most consistent and directionally specific uncertainty response to class imbalance and out-of-distribution data in the tested settings, and mark the corrupted classes under label noise, at a higher computational and tuning cost. MC-dropout matches them on the sequence data, but is uncertain about every cell on the single-cell data, and deep ensembles respond less specifically. Moreover, we show how uncertainty scores can be used to select high-quality predictions in protein--RNA interactions.

cs.LG↗

arXiv2026

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.

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arXiv2026

BASILISC: Bayesian Alignment of Siamese-Integrated Latents for Inferring Single-cell Correspondence

Single-cell assays study the genome one cell at a time. Unimodal assays measure one molecular layer, the newer multimodal assays measure several. Most data are single-modality, so integrating them relies on models trained on multimodal assays, where the cell correspondence across modalities is known. These models return a matching, but rarely a confidence measure. We present BASILISC (Bayesian Alignment of Siamese-Integrated Latents for Inferring Single-cell Correspondence), a framework for matching single-cell representations with uncertainty on the correspondence itself. A BASILISC model is a probabilistic siamese network over the two modalities with a predictive distribution over the correspondence for a cross-modal pair of cells. We instantiate it at two levels: at the cell-type level the question is whether two cells share a cell type, at the cell level which cell is the partner in the other modality. To our knowledge, this is the first uncertainty score on a learned cross-modal correspondence evaluated against a known ground-truth pairing. BASILISC learns a similarity across modalities that reflects cell lineage: an unseen cell type is matched to its lineage relative, matching still works on such held-out types (balanced accuracy 0.86 on unseen against 0.93 on seen types), and the predictive uncertainty rises on these out-of-distribution cells. The uncertainty score also selects high-quality matches for downstream analysis: discarding the least certain fifth of the pairs raises accuracy from 0.93 to 0.98. At the cell level, a deep ensemble of the deterministic matcher reaches 0.062 matching accuracy on the benchmark test set, above the competition winner; on the Bayesian matcher's assignment, the posterior flags the wrong matches that cross a cell-type boundary better than a deterministic read of the same scores (AUROC 0.68 against 0.64).

cs.LG↗

arXiv2024

Insights, opportunities and challenges provided by large cell atlases

The field of single-cell biology is growing rapidly and is generating large amounts of data from a variety of species, disease conditions, tissues, and organs. Coordinated efforts such as CZI CELLxGENE, HuBMAP, Broad Institute Single Cell Portal, and DISCO, allow researchers to access large volumes of curated datasets. Although the majority of the data is from scRNAseq experiments, a wide range of other modalities are represented as well. These resources have created an opportunity to build and expand the computational biology ecosystem to develop tools necessary for data reuse, and for extracting novel biological insights. Here, we highlight achievements made so far, areas where further development is needed, and specific challenges that need to be overcome.

q-bio.GN↗

arXiv2024

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

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arXiv2020

Deep learning for prediction of population health costs

Accurate prediction of healthcare costs is important for optimally managing health costs. However, methods leveraging the medical richness from data such as health insurance claims or electronic health records are missing. Here, we developed a deep neural network to predict future cost from health insurance claims records. We applied the deep network and a ridge regression model to a sample of 1.4 million German insurants to predict total one-year health care costs. Both methods were compared to Morbi-RSA models with various performance measures and were also used to predict patients with a change in costs and to identify relevant codes for this prediction. We showed that the neural network outperformed the ridge regression as well as all Morbi-RSA models for cost prediction. Further, the neural network was superior to ridge regression in predicting patients with cost change and identified more specific codes. In summary, we showed that our deep neural network can leverage the full complexity of the patient records and outperforms standard approaches. We suggest that the better performance is due to the ability to incorporate complex interactions in the model and that the model might also be used for predicting other health phenotypes.

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