Biology subjects

Chinwalla, A.

Publications and source records attributed to Chinwalla, A..

4 recordsLinked to original sources

bioRxiv2026

ddkg.skill: A Compositional Agent Skill for Translating Biomedical and Bioinformatics Questions into Cypher for the Data Distillery Knowledge Graph

Biomedical knowledge graphs can connect information across genes, phenotypes, tissues, pathways, experiments, and clinical resources, but they are difficult to query correctly without detailed knowledge of the graph. Large language models can help write Cypher code for knowledge graphs, yet a query focused on a bioinformatics task that looks reasonable may still use the wrong identifier, relationship direction, source, intermediate node, or output unit if the user is not completely trained on the schema. We developed ddkg.skill, an Agent Skill that can be loaded into a compatible LLM session to support querying of the NIH Common Fund Data Ecosystem Data Distillery Knowledge Graph (DDKG), a biomedical property graph integrating more than 180 ontologies, over 40 genomics datasets, and dozens of additional cross-domain biomedical datasets. Rather than utilizing a simple markdown prompt, ddkg.skill contains a controller, a compositional library of DDKG-specific references and structured tables, primary documentation, validated query patterns, a routing table, and a Python script that checks the internal links among these materials. The skill build for the December 2025 DDKG release contains 38 bundled files and 239 routing relationships and is identified by checksum so users can state the exact build used to compose a query. The evaluation reported here was performed separately on an earlier build with 38 files and 227 routing entries. In that orthogonal nine-test evaluation against a live December 2025 DDKG instance, five of seven tests targeting sources absent from the worked examples produced correct executed results. The evaluation also exposed a failed query, a cross-source comparison that was not biologically well posed, and errors in the skills own reference material that informed later revisions. The skill guides an AI through entity resolution, graph inspection, query construction, and validation for biomedical and bioinformatics queries, while keeping the DDKG itself as the source of returned results. This design provides a portable and versioned method for giving general-purpose AI systems practical knowledge of a complex biomedical knowledge graph to empower complex bioinformatics data integration. Three executed biomedical use cases further demonstrate cross-species phenotype-to-expression querying, genomic overlap between 4DN chromatin-loop anchors and GTEx eQTLs, and integration of congenital heart phenotype associations with ClinVar and GTEx heart evidence.

bioinformatics↗

bioRxiv2026

MOSAIC: Learning Graph Node Embeddings from Spectrally Isolated Dominant Subspaces of Accumulated Diffusion Operators

Graph embedding transforms complex networks into low-dimensional representations for analysis and downstream machine learning. Existing methods often rely on eigenvalue ordering, random-walk sampling, or neural optimization. We introduce MOSAIC, Multistep Operator Spectral Accumulation with Isolated Components, an unsupervised framework that constructs an accumulated diffusion operator from successive powers of a graph transition matrix. MOSAIC uses Krylov subspace analysis to identify dominant spectral components according to their convergence behavior. This approach emphasizes persistent and spectrally separated diffusion modes rather than selecting embedding coordinates solely by eigenvalue magnitude. We evaluated MOSAIC using a biomedical graph projection derived from the Data Distillery Knowledge Graph that contained 5,171 human genes and 10,147 phenotypes. Across embedding dimensions from 16 to 128, MOSAIC achieved node-type classification AUROCs from 0.9863 to 0.9926 and exceeded FastRP, Node2Vec, HashGNN, and GraphSAGE. For gene-phenotype link prediction, validation and test associations were withheld before embedding generation. Under progressive removal of all edges or specific edge classes, MOSAIC retained more node-label information than FastRP, including after extreme graph sparsification. In a focused DICER1 analysis, 106 of 137 documented phenotype associations received scores above 0.90, demonstrating concordance with known pleiotropic biology and prioritizing additional relationships for independent evaluation. These results support MOSAIC as a fully unsupervised framework for learning informative graph representations. Although demonstrated using a biomedical graph projection, MOSAIC is domain independent and can be applied to other complex networks

bioinformatics↗

bioRxiv2026

BIFO: A Biological Information Flow Ontology for Directed Propagation in Heterogeneous Biomedical Knowledge Graphs

Biomedical knowledge graphs integrate heterogeneous data by connecting many entity types through many relationship types. Computational analyses that propagate signal across these graphs (random walks, diffusion, and message passing) implicitly assume that every traversable edge can carry a biological signal. In a heterogeneous KG this is rarely true: hierarchical, lexical, and purely statistical edges do not, by themselves, define an admissible directed state transformation, and traversing them propagates signal along paths that are not biologically meaningful. We present the Biological Information Flow Ontology (BIFO), a graph-agnostic specification of which directed transformations are biologically admissible for computable information flow. BIFO defines fourteen entity classes, a taxonomy of flow classes organized around the backbone G+CH [->]RNA [->]P [->]PW [->]C [->]PH [->]DS, a set of admissibility constraints, and a two-level CURIE mapping that can be applied without schema-specific code to any graph whose identifiers and predicates are resolvable through, or extendable to, the BIFO mapping tables. A four-step conditioning protocol converts a raw property graph into a conditioned propagation graph in which only admissible, direction-aware edges remain. We provide a reference implementation on the Data Distillery Knowledge Graph (DDKG); conditioning a cohort-independent, gene-anchored subgraph as a BIFO substrate of 33.6 million edges retained 23.7 million (70.7%) as BIFO-classified relationships, cleanly separating 13.3 million propagating mechanistic edges from 10.5 million retained-but-non-propagating observational associations, and confirming that pathway concepts are configured as scoring accumulation endpoints for BIFO-PPR pathway scoring. BIFO is an admissibility specification for computable propagation of signal over knowledge graphs. It is released as an open specification with versioned mapping tables and tooling, providing a reusable substrate for biologically interpretable, direction-aware analysis of biomedical knowledge graphs.

bioinformatics↗

bioRxiv2017

RNA-Seq 2G: Online Analysis Of Differential Gene Expression With Comprehensive Options Of Statistical Methods

RNA-seq has become the most prevalent technology for measuring genome-wide gene expression, but the best practices for processing and analysing RNA-seq data are still an open question. Many statistical methods have been developed to identify genes differentially expressed between sample groups from RNA-seq data. These methods differ by their data distribution assumptions, choice of statistical test, and computational resource requirements. Over 25 methods of differential expression detection were validated and made available through a user-friendly web portal, RNA-seq 2G. All methods are suitable for analysing differential gene expression between two groups of samples. They commonly use a read count matrix derived from RNA-seq data as input and statistically compare groups for each gene. The web portal uses a Shiny app front-end and is hosted by a cloud-based server provided by Amazon Web Service. The comparison of methods showed that the data distribution assumption is the major determinant of differences between methods. Most methods are more likely to find that longer genes are differentially expressed, which substantially impacts downstream gene set-level analysis. Combining results from multiple methods can potentially diminish this bias. RNA-seq 2G makes the analysis of RNA-seq data more accessible and efficient, and is freely available at http://rnaseq2g.awsomics.org.

bioinformatics↗