arXiv subjects

Gary D. Bader

Publications and source records attributed to Gary D. Bader.

8 recordsLinked to original sources

arXiv2026

The Challenge of Cell Segmentation in Spatially Resolved Transcriptomics

Spatially resolved transcriptomics (SRT) is transforming how we study tissues by measuring gene expression in cells in their spatial context. However, the field lacks robust methodological guidance on one of its most fundamental analytical steps: how to accurately segment cells and assign spatially localized transcripts to them. Major technical challenges include sparse molecular signals, transcript displacement, complex cellular morphologies, and the projection of three-dimensional tissue architecture onto two-dimensional imaging planes. These challenges make segmentation a major source of uncertainty, with errors that can propagate through downstream analyses and ultimately lead to misleading biological interpretations. Here, we argue that segmentation should be treated as a central unresolved problem in spatial omics rather than a routine preprocessing step. We review current approaches, highlight key methodological limitations, including the lack of appropriate metrics and gold-standard benchmarks, and propose a community-driven path forward. Establishing shared evaluation frameworks, scalable benchmark datasets, and transparent reporting standards will be essential for transforming SRT into a robust and reproducible foundation for biological discovery and clinical translation.

q-bio.OT↗

arXiv2024

The Multi-modality Cell Segmentation Challenge: Towards Universal Solutions

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

eess.IV↗

arXiv2023

Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning

Histology imaging is an important tool in medical diagnosis and research, enabling the examination of tissue structure and composition at the microscopic level. Understanding the underlying molecular mechanisms of tissue architecture is critical in uncovering disease mechanisms and developing effective treatments. Gene expression profiling provides insight into the molecular processes underlying tissue architecture, but the process can be time-consuming and expensive. We present BLEEP (Bi-modaL Embedding for Expression Prediction), a bi-modal embedding framework capable of generating spatially resolved gene expression profiles of whole-slide Hematoxylin and eosin (H&E) stained histology images. BLEEP uses contrastive learning to construct a low-dimensional joint embedding space from a reference dataset using paired image and expression profiles at micrometer resolution. With this approach, the gene expression of any query image patch can be imputed using the expression profiles from the reference dataset. We demonstrate BLEEP's effectiveness in gene expression prediction by benchmarking its performance on a human liver tissue dataset captured using the 10x Visium platform, where it achieves significant improvements over existing methods. Our results demonstrate the potential of BLEEP to provide insights into the molecular mechanisms underlying tissue architecture, with important implications in diagnosis and research of various diseases. The proposed approach can significantly reduce the time and cost associated with gene expression profiling, opening up new avenues for high-throughput analysis of histology images for both research and clinical applications.

cs.CV↗

arXiv2023

Drugst.One -- A plug-and-play solution for online systems medicine and network-based drug repurposing

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

q-bio.QM↗

arXiv2022

A sequence-to-sequence approach for document-level relation extraction

Motivated by the fact that many relations cross the sentence boundary, there has been increasing interest in document-level relation extraction (DocRE). DocRE requires integrating information within and across sentences, capturing complex interactions between mentions of entities. Most existing methods are pipeline-based, requiring entities as input. However, jointly learning to extract entities and relations can improve performance and be more efficient due to shared parameters and training steps. In this paper, we develop a sequence-to-sequence approach, seq2rel, that can learn the subtasks of DocRE (entity extraction, coreference resolution and relation extraction) end-to-end, replacing a pipeline of task-specific components. Using a simple strategy we call entity hinting, we compare our approach to existing pipeline-based methods on several popular biomedical datasets, in some cases exceeding their performance. We also report the first end-to-end results on these datasets for future comparison. Finally, we demonstrate that, under our model, an end-to-end approach outperforms a pipeline-based approach. Our code, data and trained models are available at {\url{https://github.com/johngiorgi/seq2rel}}. An online demo is available at {\url{https://share.streamlit.io/johngiorgi/seq2rel/main/demo.py}}.

cs.CL↗

arXiv2019

End-to-end Named Entity Recognition and Relation Extraction using Pre-trained Language Models

Named entity recognition (NER) and relation extraction (RE) are two important tasks in information extraction and retrieval (IE \& IR). Recent work has demonstrated that it is beneficial to learn these tasks jointly, which avoids the propagation of error inherent in pipeline-based systems and improves performance. However, state-of-the-art joint models typically rely on external natural language processing (NLP) tools, such as dependency parsers, limiting their usefulness to domains (e.g. news) where those tools perform well. The few neural, end-to-end models that have been proposed are trained almost completely from scratch. In this paper, we propose a neural, end-to-end model for jointly extracting entities and their relations which does not rely on external NLP tools and which integrates a large, pre-trained language model. Because the bulk of our model's parameters are pre-trained and we eschew recurrence for self-attention, our model is fast to train. On 5 datasets across 3 domains, our model matches or exceeds state-of-the-art performance, sometimes by a large margin.

cs.CL↗

arXiv2015

SIREN Cytoscape plugin: Interaction Type Discrimination in Gene Regulatory Networks

Integrating expression data with gene interactions in a network is essential for understanding the functional organization of the cells. Consequently, knowledge of interaction types in biological networks is important for data interpretation. Signing of Regulatory Networks (SIREN) plugin for Cytoscape is an open-source Java tool for discrimination of interaction type (activatory or inhibitory) in gene regulatory networks. Utilizing an information theory based concept, SIREN seeks to identify the interaction type of pairs of genes by examining their corresponding gene expression profiles. We introduce SIREN, a fast and memory efficient tool with low computational complexity, that allows the user to easily consider it as a complementary approach for many network reconstruction methods. SIREN allows biologists to use independent expression data to predict interaction types for known gene regulatory networks where reconstruction methods do not provide any information about the nature of their interaction types. The SIREN Cytoscape plugin is implemented in Java and is freely available at http://baderlab.org/Software/SIRENplugin and via the Cytoscape app manager.

q-bio.MN↗

arXiv2011

The human genome and drug discovery after a decade. Roads (still) not taken

The draft sequence of the human genome became available almost a decade ago but the encoded proteome is not being explored to its fullest. Our bibliometric analysis of several large protein families, including those known to be "druggable", reveals that, even today, most papers focus on proteins that were known prior to 2000. It is evident that one or more aspects of the biomedical research system severely limits the exploration of the proteins in the 'dark matter' of the proteome, despite unbiased genetic approaches that have pointed to their functional relevance. It is perhaps not surprising that relatively few genome-derived targets have led to approved drugs.

q-bio.OT↗