Nicolas Deutschmann

Mara Graziani, Niccolò Marini, Nicolas Deutschmann et al.

Interpretability of deep learning is widely used to evaluate the reliability of medical imaging models and reduce the risks of inaccurate patient recommendations. For models exceeding human performance, e.g. predicting RNA structure from microscopy images, interpretable modelling can be further used to uncover highly non-trivial patterns which are otherwise imperceptible to the human eye. We show that interpretability can reveal connections between the microscopic appearance of cancer tissue and its gene expression profiling. While exhaustive profiling of all genes from the histology images is still challenging, we estimate the expression values of a well-known subset of genes that is indicative of cancer molecular subtype, survival, and treatment response in colorectal cancer. Our approach successfully identifies meaningful information from the image slides, highlighting hotspots of high gene expression. Our method can help characterise how gene expression shapes tissue morphology and this may be beneficial for patient stratification in the pathology unit. The code is available on GitHub.

Nicolas Deutschmann, Marvin Alberts, María Rodríguez Martínez

We introduce two new extensions to the beam search algorithm based on conformal predictions (CP) to produce sets of sequences with theoretical coverage guarantees. The first method is very simple and proposes dynamically-sized subsets of beam search results but, unlike typical CP procedures, has an upper bound on the achievable guarantee depending on a post-hoc calibration measure. Our second algorithm introduces the conformal set prediction procedure as part of the decoding process, producing a variable beam width which adapts to the current uncertainty. While more complex, this procedure can achieve coverage guarantees selected a priori. We provide marginal coverage bounds for each method, and evaluate them empirically on a selection of tasks drawing from natural language processing and chemistry.

Jonathan Haab, Nicolas Deutschmann, Maria Rodríguez Martínez

The debate around the interpretability of attention mechanisms is centered on whether attention scores can be used as a proxy for the relative amounts of signal carried by sub-components of data. We propose to study the interpretability of attention in the context of set machine learning, where each data point is composed of an unordered collection of instances with a global label. For classical multiple-instance-learning problems and simple extensions, there is a well-defined "importance" ground truth that can be leveraged to cast interpretation as a binary classification problem, which we can quantitatively evaluate. By building synthetic datasets over several data modalities, we perform a systematic assessment of attention-based interpretations. We find that attention distributions are indeed often reflective of the relative importance of individual instances, but that silent failures happen where a model will have high classification performance but attention patterns that do not align with expectations. Based on these observations, we propose to use ensembling to minimize the risk of misleading attention-based explanations.

Nicolas Deutschmann, Constance Ferragu, Jonathan D. Ziegler et al.

We introduce EvoFlows, a variable-length sequence-to-sequence protein modeling approach uniquely suited to protein engineering. Unlike autoregressive and masked language models, EvoFlows perform a limited, controllable number of insertions, deletions, and substitutions on a template protein sequence. In other words, EvoFlows predict not only _which_ mutation to perform, but also _where_ it should occur. Our approach leverages edit flows to learn mutational trajectories between evolutionarily-related protein sequences, simultaneously modeling distributions of related natural proteins and the mutational paths connecting them. Through extensive _in silico_ evaluation on diverse protein communities from UNIREF and OAS, we demonstrate that EvoFlows capture protein sequence distributions with a quality comparable to leading masked language models commonly used in protein engineering, while showing improved ability to generate non-trivial yet natural-like mutants from a given template protein.

Constance Ferragu, Jonathan D. Ziegler, Nicolas Deutschmann et al.

Direct Preference Optimization (DPO) is an effective approach for aligning protein language models with experimental design goals. However, DPO faces a scalability bottleneck: the number of possible training pairs grows quadratically with the number of labeled sequences, leading to prohibitive training times even for modestly sized datasets. We introduce g-DPO, a framework that (i) uses sequence space clustering to prune redundant pairs while preserving training signal, and (ii) amortizes likelihood computations with group-based approximations. Across three protein engineering tasks, g-DPO maintains in-silico and in-vitro performance that is statistically indistinguishable from standard DPO, while converging 1.8 to 3.7 times faster, with greater gains expected as the size of the dataset increases.

Nicolas Deutschmann, Mattia Rigotti, Maria Rodriguez Martinez

Conformal regression provides prediction intervals with global coverage guarantees, but often fails to capture local error distributions, leading to non-homogeneous coverage. We address this with a new adaptive method based on rescaling conformal scores with an estimate of local score distribution, inspired by the Jackknife+ method, which enables the use of calibration data in conformal scores without breaking calibration-test exchangeability. Our approach ensures formal global coverage guarantees and is supported by new theoretical results on local coverage, including an a posteriori bound on any calibration score. The strength of our approach lies in achieving local coverage without sacrificing calibration set size, improving the applicability of conformal prediction intervals in various settings. As a result, our method provides prediction intervals that outperform previous methods, particularly in the low-data regime, making it especially relevant for real-world applications such as healthcare and biomedical domains where uncertainty needs to be quantified accurately despite low sample data.