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Valentina Boeva

Publications and source records attributed to Valentina Boeva.

11 recordsLinked to original sources

DistillPath: An Efficient 22M Distilled Pathology Encoder Approaching Large Foundation Model Performance

Many high-performing pathology tile encoders are now foundation models with hundreds of millions to over a billion parameters. Encoding and storing the thousands of tiles in each whole-slide image with such models is costly on commodity hardware, so compact encoders that retain useful downstream performance are a valuable alternative. We present DistillPath-KS16, which starts from the existing 22M kaiko ViT-S/16 encoder and improves it by distilling from released pathology encoders used as frozen teachers. The recipe reads only the teachers' final class and patch tokens and trains on 6,000 public slides, needing neither their DINO nor iBOT pretraining heads nor a billion-tile corpus, so it applies to any released encoder that exposes backbone tokens. We distill four teachers spanning 86M to 1.1B parameters into the same student. Every variant improves the kaiko baseline on all three benchmarks we use, EVA, HEST, and PLISM, and the strongest teacher is task-dependent. On the seven-task EVA mean, DistillPath-KS16-Virchow2 reaches $0.795$, within $0.015$ points of Virchow2, the top-scoring model in our evaluation, at about $29\times$ fewer parameters; it also scores above H0-mini and GPFM on this aggregate metric, though that advantage is task-concentrated rather than uniform. Because it remains a 22M ViT-S/16 with 384-dimensional features, DistillPath-KS16 runs more than $25\times$ faster than Virchow2. Code is available at https://github.com/RamonKaspar/DistillPath, and released model weights are available at https://huggingface.co/collections/RamonK/distillpath.

cs.CV

Fixed-Point Reasoners: Stable and Adaptive Deep Looped Transformers

Looped architectures provide an inductive bias toward learning step-by-step procedures for tasks that require compositional reasoning. The number of effective layers reached by looping determines the quality of the solution these models find. Like deep architectures, looped architectures are prone to a signal propagation problem induced by depth as the halting decision is postponed. In this paper, we address this signal propagation issue using pre-norm layers and residual scaling. Building on these architectural modifications, we propose FPRM, a Transformer-based Fixed-Point Reasoning Model that uses fixed-point convergence as an end-to-end halting mechanism in a looped architecture. We show that fixed-point halting allows FPRM to adapt its compute to task difficulty. FPRM is effective on common reasoning benchmarks, namely Sudoku, Maze, state-tracking, and ARC-AGI.

cs.AI

Generalized Linear Mode Connectivity for Transformers

Understanding the geometry of neural network loss landscapes is a central question in deep learning, with implications for generalization and optimization. A striking phenomenon is linear mode connectivity (LMC), where independently trained models can be connected by low- or zero-loss paths despite appearing to lie in separate loss basins. However, this is often obscured by symmetries in parameter space -- such as neuron permutations -- which make functionally equivalent models appear dissimilar. Prior work has predominantly focused on neuron reordering through permutations, but such approaches are limited in scope and fail to capture the richer symmetries exhibited by modern architectures such as Transformers. In this work, we introduce a unified framework that captures four symmetry classes -- permutations, semi-permutations, orthogonal transformations, and general invertible maps -- broadening the set of valid reparameterizations and subsuming many previous approaches as special cases. Crucially, this generalization enables, for the first time, the discovery of low- and zero-barrier linear interpolation paths between independently trained Vision Transformers and GPT-2 models. Furthermore, our framework extends beyond pairwise alignment to multi-model and width-heterogeneous settings, enabling alignment across architectures of different sizes. These results reveal deeper structure in the loss landscape and underscore the importance of symmetry-aware analysis for understanding model space geometry.

cs.LG

scSSL-Bench: Benchmarking Self-Supervised Learning for Single-Cell Data

Self-supervised learning (SSL) has proven to be a powerful approach for extracting biologically meaningful representations from single-cell data. To advance our understanding of SSL methods applied to single-cell data, we present scSSL-Bench, a comprehensive benchmark that evaluates nineteen SSL methods. Our evaluation spans nine datasets and focuses on three common downstream tasks: batch correction, cell type annotation, and missing modality prediction. Furthermore, we systematically assess various data augmentation strategies. Our analysis reveals task-specific trade-offs: the specialized single-cell frameworks, scVI, CLAIRE, and the finetuned scGPT excel at uni-modal batch correction, while generic SSL methods, such as VICReg and SimCLR, demonstrate superior performance in cell typing and multi-modal data integration. Random masking emerges as the most effective augmentation technique across all tasks, surpassing domain-specific augmentations. Notably, our results indicate the need for a specialized single-cell multi-modal data integration framework. scSSL-Bench provides a standardized evaluation platform and concrete recommendations for applying SSL to single-cell analysis, advancing the convergence of deep learning and single-cell genomics.

q-bio.QM

Feature Clock: High-Dimensional Effects in Two-Dimensional Plots

Humans struggle to perceive and interpret high-dimensional data. Therefore, high-dimensional data are often projected into two dimensions for visualization. Many applications benefit from complex nonlinear dimensionality reduction techniques, but the effects of individual high-dimensional features are hard to explain in the two-dimensional space. Most visualization solutions use multiple two-dimensional plots, each showing the effect of one high-dimensional feature in two dimensions; this approach creates a need for a visual inspection of k plots for a k-dimensional input space. Our solution, Feature Clock, provides a novel approach that eliminates the need to inspect these k plots to grasp the influence of original features on the data structure depicted in two dimensions. Feature Clock enhances the explainability and compactness of visualizations of embedded data and is available in an open-source Python library.

cs.LG

Histopathological Image Classification with Cell Morphology Aware Deep Neural Networks

Histopathological images are widely used for the analysis of diseased (tumor) tissues and patient treatment selection. While the majority of microscopy image processing was previously done manually by pathologists, recent advances in computer vision allow for accurate recognition of lesion regions with deep learning-based solutions. Such models, however, usually require extensive annotated datasets for training, which is often not the case in the considered task, where the number of available patient data samples is very limited. To deal with this problem, we propose a novel DeepCMorph model pre-trained to learn cell morphology and identify a large number of different cancer types. The model consists of two modules: the first one performs cell nuclei segmentation and annotates each cell type, and is trained on a combination of 8 publicly available datasets to ensure its high generalizability and robustness. The second module combines the obtained segmentation map with the original microscopy image and is trained for the downstream task. We pre-trained this module on the Pan-Cancer TCGA dataset consisting of over 270K tissue patches extracted from 8736 diagnostic slides from 7175 patients. The proposed solution achieved a new state-of-the-art performance on the dataset under consideration, detecting 32 cancer types with over 82% accuracy and outperforming all previously proposed solutions by more than 4%. We demonstrate that the resulting pre-trained model can be easily fine-tuned on smaller microscopy datasets, yielding superior results compared to the current top solutions and models initialized with ImageNet weights. The codes and pre-trained models presented in this paper are available at: https://github.com/aiff22/DeepCMorph

eess.IV

scTree: Discovering Cellular Hierarchies in the Presence of Batch Effects in scRNA-seq Data

We propose a novel method, scTree, for single-cell Tree Variational Autoencoders, extending a hierarchical clustering approach to single-cell RNA sequencing data. scTree corrects for batch effects while simultaneously learning a tree-structured data representation. This VAE-based method allows for a more in-depth understanding of complex cellular landscapes independently of the biasing effects of batches. We show empirically on seven datasets that scTree discovers the underlying clusters of the data and the hierarchical relations between them, as well as outperforms established baseline methods across these datasets. Additionally, we analyze the learned hierarchy to understand its biological relevance, thus underpinning the importance of integrating batch correction directly into the clustering procedure.

cs.LG

Ococo: an online variant and consensus caller

Motivation: Identifying genomic variants is an essential step for connecting genotype and phenotype. The usual approach consists of statistical inference of variants from alignments of sequencing reads. State-of-the-art variant callers can resolve a wide range of different variant types with high accuracy. However, they require that all read alignments be available from the beginning of variant calling and be sorted by coordinates. Sorting is computationally expensive, both memory- and speed-wise, and the resulting pipelines suffer from storing and retrieving large alignments files from external memory. Therefore, there is interest in developing methods for resource-efficient variant calling. Results: We present Ococo, the first program capable of inferring variants in a real-time, as read alignments are fed in. Ococo inputs unsorted alignments from a stream and infers single-nucleotide variants, together with a genomic consensus, using statistics stored in compact several-bit counters. Ococo provides a fast and memory-efficient alternative to the usual variant calling. It is particularly advantageous when reads are sequenced or mapped progressively, or when available computational resources are at a premium.

q-bio.GN

Dynamic read mapping and online consensus calling for better variant detection

Variant detection from high-throughput sequencing data is an essential step in identification of alleles involved in complex diseases and cancer. To deal with these massive data, elaborated sequence analysis pipelines are employed. A core component of such pipelines is a read mapping module whose accuracy strongly affects the quality of resulting variant calls. We propose a dynamic read mapping approach that significantly improves read alignment accuracy. The general idea of dynamic mapping is to continuously update the reference sequence on the basis of previously computed read alignments. Even though this concept already appeared in the literature, we believe that our work provides the first comprehensive analysis of this approach. To evaluate the benefit of dynamic mapping, we developed a software pipeline (http://github.com/karel-brinda/dymas) that mimics different dynamic mapping scenarios. The pipeline was applied to compare dynamic mapping with the conventional static mapping and, on the other hand, with the so-called iterative referencing - a computationally expensive procedure computing an optimal modification of the reference that maximizes the overall quality of all alignments. We conclude that in all alternatives, dynamic mapping results in a much better accuracy than static mapping, approaching the accuracy of iterative referencing. To correct the reference sequence in the course of dynamic mapping, we developed an online consensus caller named OCOCO (http://github.com/karel-brinda/ococo). OCOCO is the first consensus caller capable to process input reads in the online fashion. Finally, we provide conclusions about the feasibility of dynamic mapping and discuss main obstacles that have to be overcome to implement it. We also review a wide range of possible applications of dynamic mapping with a special emphasis on variant detection.

q-bio.GN

RNF: a general framework to evaluate NGS read mappers

Aligning reads to a reference sequence is a fundamental step in numerous bioinformatics pipelines. As a consequence, the sensitivity and precision of the mapping tool, applied with certain parameters to certain data, can critically affect the accuracy of produced results (e.g., in variant calling applications). Therefore, there has been an increasing demand of methods for comparing mappers and for measuring effects of their parameters. Read simulators combined with alignment evaluation tools provide the most straightforward way to evaluate and compare mappers. Simulation of reads is accompanied by information about their positions in the source genome. This information is then used to evaluate alignments produced by the mapper. Finally, reports containing statistics of successful read alignments are created. In default of standards for encoding read origins, every evaluation tool has to be made explicitly compatible with the simulator used to generate reads. In order to solve this obstacle, we have created a generic format RNF (Read Naming Format) for assigning read names with encoded information about original positions. Futhermore, we have developed an associated software package RNF containing two principal components. MIShmash applies one of popular read simulating tools (among DwgSim, Art, Mason, CuReSim etc.) and transforms the generated reads into RNF format. LAVEnder evaluates then a given read mapper using simulated reads in RNF format. A special attention is payed to mapping qualities that serve for parametrization of ROC curves, and to evaluation of the effect of read sample contamination.

q-bio.GN

Deciphering regulation in eukaryotic cell: from sequence to function

A transversal topic of my research has been the development and application of computational methods for DNA sequence analysis. The methods I have been developing aim at improving our understanding of the regulation processes happening in normal and cancer cells. This topic connects together the projects presented in this thesis. Two chapters of the thesis represent major areas of my research interests: (1) methods for deciphering transcriptional regulation and their application to answer specific biological questions, and (2) methods to study the genome structure and their application in cancer studies. The first chapter predominantly focuses on transcriptional regulation. Here I describe my contribution to the development of methodology for the discovery of transcription factor binding sites and the positioning of histone proteins. I also explain how sequence analysis, in combination with gene expression data, can allow the identification of direct target genes of a transcription factor under study, as well as the physical mechanisms of its action. As two examples, I provide the results of my study of transcriptional regulation by (i) oncogenic protein EWS-FLI1 in Ewing sarcoma and (ii) oncogenic transcription factor Spi-1/PU.1 in erythroleukemia. In the second chapter, I describe the sequence analysis methods aimed at the identification of the genomic rearrangements in species with existing reference genome. I explain how the developed methodology can be applied to detect the structure of cancer genomes. I provide an example of how such an analysis of tumor genomes can result in a discovery of a new phenomenon: chromothripsis, when hundreds of rearrangements occur in a single cellular catastrophe. The thesis is concluded by listing the major challenges in high-throughput sequencing analysis. I also discuss the current top questions demanding the integration of sequencing data.

q-bio.GN