Sepulveda-Yanez, J. | Search bioRxiv

bioRxiv2026

SilkRoute: A Descriptor-Driven Framework for Reproducible Multi-Source Biomolecular Data Acquisition

BackgroundBiomolecular dataset construction often requires coordinated retrieval from heterogeneous repositories, identifier mapping, cross-reference enrichment, source-specific parsing, and provenance recording. These operations are frequently implemented through project-specific scripts, making acquisition procedures difficult to inspect, reproduce, or adapt across studies. We present SilkRoute, an open-source Python framework that formalizes biomolecular data acquisition as descriptor-defined, source-aware, and provenance-tracked workflows, providing a reproducible foundation for multi-source biomolecular dataset construction. ResultsSilkRoute uses machine-readable YAML descriptors to specify dataset intent, biomolecular modality, workflow mode, query logic, enrichment resources, execution parameters, and export settings. These descriptors drive a common execution model that coordinates primary retrieval and downstream enrichment while preserving source-specific outputs, interaction evidence when available, the original workflow configuration, metadata, and run summaries. We evaluated this model through three representative acquisition scenarios spanning proteins, compounds, and molecular interactions. In the protein-centered workflow, SilkRoute retrieved 2,444 reviewed antimicrobial protein records from UniProt and generated complementary outputs from AlphaFold DB, InterPro, Pathway Commons, and the Protein Data Bank. In the compound-centered workflow, a ChEMBL IC50 query produced 1,445,939 activity records organized into query-defined potency ranges. In the interaction-centered workflow, 2,253 UniProt protein records were expanded with 902,713 BioGRID interaction records and 5,702 STRING interaction-partner records. Across these scenarios, the framework successfully applied the same descriptor-defined acquisition model to distinct biomolecular entity types, retrieval strategies, enrichment paths, and output structures. ConclusionsSilkRoute extends beyond sequence retrieval by providing a reusable acquisition layer for constructing multi-source biomolecular datasets. By separating primary retrieval from enrichment and preserving source-aware outputs together with workflow descriptors and execution metadata, the framework makes acquisition procedures easier to inspect, reproduce, archive, and adapt. SilkRoute does not replace biological curation, label validation, deduplication, partitioning, or benchmarking, but provides structured and traceable acquisition packages that support these downstream processes.

bioinformatics↗

bioRxiv2020

CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells

BackgroundDrawing genotype-to-phenotype maps in tumors is of paramount importance for understanding tumor heterogeneity. Assignment of single cells to their tumor clones of origin can be approached by matching the genotypes of the clones to the mutations found in RNA sequencing of the cells. The confidence of the cell-to-clone mapping can be increased by accounting for additional measurements. Follicular lymphoma, a malignancy of mature B cells that continuously acquire mutations in parallel in the exome and in B-cell receptor loci, presents a unique opportunity to align exome-derived mutations with B-cell receptor clonotypes as an independent measure for clonal evolution. ResultsHere, we propose CACTUS, a probabilistic model that leverages the information from an independent genomic clustering of cells and exploits the scarce single cell RNA sequencing data to map single cells to given imperfect genotypes of tumor clones. We apply CACTUS to two follicular lymphoma patient samples, integrating three measurements: whole exome sequencing, single cell RNA sequencing, and B-cell receptor sequencing. CACTUS outperforms a predecessor model by confidently assigning cells and B-cell receptor clonotypes to the tumor clones. ConclusionsThe integration of independent measurements increases model certainty and is the key to improving model performance in the challenging task of charting the genotype-to-phenotype maps in tumors. CACTUS opens the avenue to study the functional implications of tumor heterogeneity, and origins of resistance to targeted therapies.

cancer biology↗