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Andreas Bjerregaard

Publications and source records attributed to Andreas Bjerregaard.

4 recordsLinked to original sources

BEND 2.0: Benchmarking the Capabilities Needed to Design DNA

Genomic foundation models are increasingly used to propose DNA sequences and edits. But successful design requires capabilities that current benchmarks do not measure. Here we introduce BEND 2.0 (BENchmark for DNA language models), which tests how well models predict the effects of DNA changes and whether these predictions can guide sequence design. Across eight tasks built on five experimental datasets, we find that model choice and how representations are accessed both affect performance. Linear readouts fitted to frozen representations can match or exceed models' native outputs, and functional post-training substantially improves the models' capabilities. Linear readouts transfer well across experimental assays and genes, suggesting that models capture functional patterns beyond the data used to fit individual predictors. At the same time, strong prediction of average effects can conceal weaker prediction of context-specific effects, and accurate prediction of combined mutation effects does not imply accurate prediction of their interactions. In design tasks, model predictions can reduce the number of candidates needed to find a desired response, but still leave substantial room for better design choices, particularly for context-specific and multi-cell objectives. Our benchmark reveals that genomic models now display signs of general utility but have yet to saturate on performance in even simple tasks.

q-bio.GN↗

RAGenome: Scaling Retrieval-Based Genomic Language Models to Long Contexts

The genome holds the blueprint that governs the biological properties of the cell. Consequently, advancing our knowledge of genomic function is crucial both for a broader understanding of biology and for continued biomedical advances. The success of large language models on natural language and protein sequences has motivated similar efforts on genomic data. However, standard genomic language models (gLMs) often require extremely large computational resources and still fall behind traditional methods on some downstream tasks. Recently, MSA-based pretraining has been proposed as an efficient alternative, but existing models are limited to short input contexts, restricting their use to short-range tasks, such as variant effect prediction. In this work, we present RAGenome, the first retrieval-based gLM that scales pretraining to longer contexts (100$\times$ longer than existing MSA-based gLMs), allowing it to capture both across-species evolutionary relationships and within-species longer-range interactions. Trained on whole-genome alignments from 100 vertebrates, RAGenome substantially improves the long-range capabilities of MSA-based gLMs, raising gene finding performance from 0.45 to 0.60, while remaining competitive on purely evolutionary-based tasks like prioritizing pathogenic variants. RAGenome provides competitive gLM performance at a fraction of the training cost, unifying evolutionary modeling and long-range capabilities within a single, flexible, scalable framework. Code is available at https://github.com/PanosAntoniadis/RAGenome.

cs.LG↗

Riemannian Generative Decoder

Euclidean representations distort data with intrinsic non-Euclidean structure. While Riemannian representation learning offers a solution by embedding data onto matching manifolds, it typically relies on an encoder to estimate densities on chosen manifolds. This involves optimizing numerically brittle objectives, potentially harming model training and quality. To completely circumvent this issue, we introduce the Riemannian generative decoder, a unifying approach for finding manifold-valued latents on any Riemannian manifold. Latents are learned with a Riemannian optimizer while jointly training a decoder network. By discarding the encoder, we vastly simplify the manifold constraint compared to current approaches which often only handle few specific manifolds. We validate our approach on three case studies -- a synthetic branching diffusion process, human migrations inferred from mitochondrial DNA, and cells undergoing a cell division cycle -- each showing that learned representations respect the prescribed geometry and capture intrinsic non-Euclidean structure. Our method requires only a decoder, is compatible with existing architectures, and yields interpretable latent spaces aligned with data geometry. Code available on https://github.com/yhsure/riemannian-generative-decoder.

cs.LG↗

Attenuation-adjusted deep learning of pore defects in 2D radiographs of additive manufacturing powders

The presence of gas pores in metal feedstock powder for additive manufacturing greatly affects the final AM product. Since current porosity analysis often involves lengthy X-ray computed tomography (XCT) scans with a full rotation around the sample, motivation exists to explore methods that allow for high throughput -- possibly enabling in-line porosity analysis during manufacturing. Through labelling pore pixels on single 2D radiographs of powders, this work seeks to simulate such future efficient setups. High segmentation accuracy is achieved by combining a model of X-ray attenuation through particles with a variant of the widely applied UNet architecture; notably, F1-score increases by $11.4\%$ compared to the baseline UNet. The proposed pore segmentation is enabled by: 1) pretraining on synthetic data, 2) making tight particle cutouts, and 3) subtracting an ideal particle without pores generated from a distance map inspired by Lambert-Beers law. This paper explores four image processing methods, where the fastest (yet still unoptimized) segments a particle in mean $0.014s$ time with F1-score $0.78$, and the most accurate in $0.291s$ with F1-score $0.87$. Due to their scalable nature, these strategies can be involved in making high throughput porosity analysis of metal feedstock powder for additive manufacturing.

cs.CV↗