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/.