Search arXivSearch

arXiv · 2604.12387

oxo-call: Documentation-grounded Skill Augmentation for Accurate Bioinformatics Command-line Generation with Large Language Models

Abstract

Command-line bioinformatics tools remain essential for genomic analysis, yet their diversity in syntax and parameterization presents a persistent barrier to productive research. We present oxo-call, a Rust-based command-line assistant that translates natural-language task descriptions into accurate tool invocations through two complementary strategies: documentation-first grounding, which provides the large language model (LLM) with the complete, version-specific help text of each target tool, and curated skill augmentation, which primes the model with domain-expert concepts, common pitfalls, and worked examples. oxo-call (v0.10) ships >150 built-in skills covering 44 analytical categories, from variant calling and genome assembly to single-cell transcriptomics, compiled into a single, statically linked binary. Every generated command is logged with provenance metadata to support reproducible research. oxo-call also provides a DAG-based workflow engine, extensibility through user-defined and community skills via the Model Context Protocol, and support for local LLM inference to address data-privacy requirements. oxo-call is freely available for academic use at https://traitome.github.io/oxo-call/.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yun Peng, Yujun Sun, Jia Ding, Bin Yan, Zhangyu Wang, Chunyang Wang, Chenyang Shu, Jian-Guo Zhou, Shixiang Wang. 2026-04-14. oxo-call: Documentation-grounded Skill Augmentation for Accurate Bioinformatics Command-line Generation with Large Language Models. https://arxiv.org/abs/2604.12387

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Revolutionizing Genomics with Reinforcement Learning Techniques

In recent years, Reinforcement Learning (RL) has emerged as a powerful tool for solving a wide range of problems, including decision-making and genomics. The exponential growth of raw genomic data over the past two decades has exceeded the capacity of manual analysis, leading to a growing interest in automatic data analysis and processing. RL algorithms are capable of learning from experience with minimal human supervision, making them well-suited for genomic data analysis and interpretation. One of the key benefits of using RL is the reduced cost associated with collecting labeled training data, which is required for supervised learning. While there have been numerous studies examining the applications of Machine Learning (ML) in genomics, this survey focuses exclusively on the use of RL in various genomics research fields, including gene regulatory networks (GRNs), genome assembly, and sequence alignment. We present a comprehensive technical overview of existing studies on the application of RL in genomics, highlighting the strengths and limitations of these approaches. We then discuss potential research directions that are worthy of future exploration, including the development of more sophisticated reward functions as RL heavily depends on the accuracy of the reward function, the integration of RL with other machine learning techniques, and the application of RL to new and emerging areas in genomics research. Finally, we present our findings and conclude by summarizing the current state of the field and the future outlook for RL in genomics.

q-bio.GN

Transcriptomic Models for Immunotherapy Response Prediction Show Limited Cross-cohort Generalisability

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; yet substantial proportion of patients exhibit intrinsic or acquired resistance, making accurate pre-treatment response prediction a critical unmet need. Transcriptomics-based biomarkers derived from bulk and single-cell RNA sequencing (scRNA-seq) offer a promising avenue for capturing tumour-immune interactions, yet the cross-cohort generalisability of existing prediction models remains unclear.We systematically benchmark nine state-of-the-art transcriptomic ICI response predictors, five bulk RNA-seq-based models (COMPASS, IRNet, NetBio, IKCScore, and TNBC-ICI) and four scRNA-seq-based models (PRECISE, DeepGeneX, Tres and scCURE), using publicly available independent datasets unseen during model development. Overall, predictive performance was modest: bulk RNA-seq models performed at or near chance level across most cohorts, while scRNA-seq models showed only marginal improvements. Pathway-level analyses revealed sparse and inconsistent biomarker signals across models. Although scRNA-seq-based predictors converged on immune-related programs such as allograft rejection, bulk RNA-seq-based models exhibited little reproducible overlap. PRECISE and NetBio identified the most coherent immune-related themes, whereas IRNet predominantly captured metabolic pathways weakly aligned with ICI biology. Together, these findings demonstrate the limited cross-cohort robustness and biological consistency of current transcriptomic ICI prediction models, underscoring the need for improved domain adaptation, standardised preprocessing, and biologically grounded model design.

q-bio.GN

Large Language Model Agents for Evidence Based Genetic Disease Severity Classification

Disease severity classification for genetic conditions is subjective and labor-intensive, creating bottlenecks in genomic screening, where commercial panels vary widely in size and overlap. We developed an autonomous AI agent integrating Reasoning and Acting (ReAct) with Retrieval-Augmented Generation (RAG) to classify 10,211 Human Phenotype Ontology terms. It uses American College of Medical Genetics (ACMG)-endorsed severity guidelines and American College of Obstetricians and Gynecologists (ACOG) quality-of-life criteria to retrieve PubMed literature, generate interpretable reasoning chains, and independently verify claims. At the phenotype level, using expert-curated cohorts, the agent achieved 93.55% accuracy (MCC 0.9237) with 82.6% to 91.4% of claims supported by direct evidence or valid inferences. Gene-level severity was aggregated across 8,738 pairs, identifying 3,283 autosomal recessive pairs with severe or profound presentations. External validation showed 95.2% concordance with Mackenzie's Mission gene list. This system enables standardized panel design by providing reliable, automated classification supported by direct evidence.

q-bio.GN