MOTIVATION: Knowledge graphs (KGs) are powerful tools for structuring and analyzing biological information due to their ability to represent data and improve queries across heterogeneous datasets. However, constructing KGs from unstructured literature remains challenging due to the cost and expertise required for manual curation. Prior works have explored text-mining techniques to automate this process, but have limitations that impact their ability to capture complex relationships fully. Traditional text-mining methods struggle with understanding context across sentences. Additionally, these methods lack expert-level background knowledge, making it difficult to infer relationships that require awareness of concepts indirectly described in the text. Large Language Models (LLMs) present an opportunity to overcome these challenges. LLMs are trained on diverse literature, equipping them with contextual knowledge that enables more accurate information extraction. RESULTS: We present textToKnowledgeGraph, an artificial intelligence tool using LLMs to extract interactions from individual publications directly in Biological Expression Language (BEL). BEL was chosen for its compact, detailed representation of biological relationships, enabling structured, computationally accessible encoding. This work makes several contributions. (i) Development of the open-source Python textToKnowledgeGraph package (pypi.org/project/texttoknowledgegraph) for BEL extraction from scientific articles, usable from the command line and within other projects, (ii) an interactive application within Cytoscape Web to simplify extraction and exploration, (iii) a dataset of extractions that have been both computationally and manually reviewed to support future fine-tuning efforts. AVAILABILITY AND IMPLEMENTATION: https://github.com/ndexbio/llm-text-to-knowledge-graph.

We present scPilot, the first systematic framework to practice \textit{omics-native reasoning}: a large language model (LLM) converses in natural language while directly inspecting single-cell RNA-seq data and on-demand bioinformatics tools. scPilot converts core single-cell analyses, i.e., cell-type annotation, developmental-trajectory reconstruction, and transcription-factor targeting, into step-by-step reasoning problems that the model must solve, justify, and, when needed, revise with new evidence. To measure progress, we release \scbench, a suite of 9 expertly curated datasets and graders that faithfully evaluate the omics-native reasoning capability of scPilot w.r.t various LLMs. Experiments with o1 show that \textit{iterative} omics-native reasoning lifts average accuracy by 11\% for cell-type annotation and Gemini 2.5 Pro cuts trajectory graph-edit distance by 30\% versus one-shot prompting, while generating transparent reasoning traces that explain marker gene ambiguity and regulatory logic. By grounding LLMs in raw omics data, scPilot enables auditable, interpretable, and diagnostically informative single-cell analyses.

SUMMARY: Cells are organized as a hierarchy of macromolecular assemblies, ranging from small protein complexes to entire organelles. Various technologies have been developed to elucidate subcellular architecture at different scales, such as mass spectrometry approaches for mapping protein biophysical interactions and immunofluorescence imaging for mapping protein localization. We present the Cell Mapping Toolkit, which is designed to systematically integrate data from different modalities into unified hierarchical maps of subcellular organization. The toolkit facilitates an end-to-end pipeline including processing datasets, integrating modalities, and visualizing the final cell map with rich metadata including provenance documentation at each step. The Cell Mapping Toolkit provides researchers with tools for analyzing, integrating, and visualizing diverse protein datasets in a robust and reproducible framework. AVAILABILITY AND IMPLEMENTATION: The code is freely available and is hosted on GitHub at https://github.com/idekerlab/cellmaps_pipeline. Comprehensive documentation and practical examples are provided at https://cellmaps-pipeline.readthedocs.io/.

MOTIVATION: The investigation of sets of genes using biological pathways is a common task for researchers and is supported by a wide variety of software tools. This type of analysis generates hypotheses about the biological processes that are active or modulated in a specific experimental context. RESULTS: The Network Data Exchange Integrated Query (NDEx IQuery) is a new tool for network and pathway-based gene set interpretation that complements or extends existing resources. It combines novel sources of pathways, integration with Cytoscape, and the ability to store and share analysis results. The NDEx IQuery web application performs multiple gene set analyses based on diverse pathways and networks stored in NDEx. These include curated pathways from WikiPathways and SIGNOR, published pathway figures from the last 27 years, machine-assembled networks using the INDRA system, and the new NCI-PID v2.0, an updated version of the popular NCI Pathway Interaction Database. NDEx IQuery's integration with MSigDB and cBioPortal now provides pathway analysis in the context of these two resources. AVAILABILITY AND IMPLEMENTATION: NDEx IQuery is available at https://www.ndexbio.org/iquery and is implemented in Javascript and Java.

MOTIVATION: A large variety of molecular interactions occurs between biomolecular components in cells. When a molecular interaction results in a regulatory effect, exerted by one component onto a downstream component, a so-called 'causal interaction' takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g. gene regulation) need to be described with a careful appreciation of the underlying molecular reactions. A proper description of this information enables archiving, sharing and reuse by humans and for automated computational processing. Various representations of causal relationships between biological components are currently used in a variety of resources. RESULTS: Here, we propose a checklist that accommodates current representations, called the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while fostering uniformity and interoperability of the data across resources. AVAILABILITY AND IMPLEMENTATION: The checklist together with examples is accessible at https://github.com/MI2CAST/MI2CAST. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Detection of community structure has become a fundamental step in the analysis of biological networks with application to protein function annotation, disease gene prediction, and drug discovery. This recent impact creates a need to make these techniques and their accompanying visualization schemes available to a broad range of biologists. Here we present a service-oriented, end-to-end software framework, CDAPS (Community Detection APplication and Service), that integrates the identification, annotation, visualization, and interrogation of multiscale network communities, accessible within the popular Cytoscape network analysis platform. With novel design principles, CDAPS addresses unmet new challenges, such as identifying hierarchical community structures, comparison of outputs generated from diverse network resources, and easy deployment of new algorithms, to facilitate community-sourced science. We demonstrate that the CDAPS framework can be applied to high-throughput protein-protein interaction networks to gain novel insights, such as the identification of putative new members of known protein complexes.

Motivation: Seamless exchange of biological network data enables bioinformatic algorithms to integrate networks as prior knowledge input as well as to document resulting network output. However, the interoperability between pathway databases and various methods and platforms for analysis is currently lacking. The Network Data Exchange (NDEx) is an open-source data commons that facilitates the user-centered sharing and publication of networks of many types and formats. Results: Here, we present a software package that allows users to programmatically connect to and interface with NDEx servers from within R. The network repository can be searched and networks can be retrieved and converted into igraph-compatible objects. These networks can be modified and extended within R and uploaded back to the NDEx servers. Availability and implementation: ndexr is a free and open-source R package, available via GitHub (https://github.com/frankkramer-lab/ndexr) and Bioconductor (http://bioconductor.org/packages/ndexr/). Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

Network propagation is an important and widely used algorithm in systems biology, with applications in protein function prediction, disease gene prioritization, and patient stratification. However, up to this point it has required significant expertise to run. Here we extend the popular network analysis program Cytoscape to perform network propagation as an integrated function. Such integration greatly increases the access to network propagation by putting it in the hands of biologists and linking it to the many other types of network analysis and visualization available through Cytoscape. We demonstrate the power and utility of the algorithm by identifying mutations conferring resistance to Vemurafenib.

BACKGROUND: Gene expression profiling and other genome-scale measurement technologies provide comprehensive information about molecular changes resulting from a chemical or genetic perturbation, or disease state. A critical challenge is the development of methods to interpret these large-scale data sets to identify specific biological mechanisms that can provide experimentally verifiable hypotheses and lead to the understanding of disease and drug action. RESULTS: We present a detailed description of Reverse Causal Reasoning (RCR), a reverse engineering methodology to infer mechanistic hypotheses from molecular profiling data. This methodology requires prior knowledge in the form of small networks that causally link a key upstream controller node representing a biological mechanism to downstream measurable quantities. These small directed networks are generated from a knowledge base of literature-curated qualitative biological cause-and-effect relationships expressed as a network. The small mechanism networks are evaluated as hypotheses to explain observed differential measurements. We provide a simple implementation of this methodology, Whistle, specifically geared towards the analysis of gene expression data and using prior knowledge expressed in Biological Expression Language (BEL). We present the Whistle analyses for three transcriptomic data sets using a publically available knowledge base. The mechanisms inferred by Whistle are consistent with the expected biology for each data set. CONCLUSIONS: Reverse Causal Reasoning yields mechanistic insights to the interpretation of gene expression profiling data that are distinct from and complementary to the results of analyses using ontology or pathway gene sets. This reverse engineering algorithm provides an evidence-driven approach to the development of models of disease, drug action, and drug toxicity.