Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Pedigree Analysis01:35

Pedigree Analysis

Overview
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Histone deacetylase enzyme activity is not the universal anticancer target of HDAC inhibitors.

Signal transduction and targeted therapy·2026
Same author

Integration of cross-species multi-omics with in vivo experimental validation identifies Parkinson's disease therapeutic targets and novel risk factors within endolysosomal pathway subnetworks.

Neurobiology of disease·2026
Same author

LA-MARRVEL: A Knowledge-Grounded, Language-Aware LLM Framework for Clinically Robust Rare Disease Gene Prioritization.

ArXiv·2026
Same author

Primate lineage specification requires suppression of Alu hyperediting.

bioRxiv : the preprint server for biology·2026
Same author

ClinPreAI: An Agentic AI System for Early Postpartum Depression Risk Prediction from Multimodal EHR Data.

medRxiv : the preprint server for health sciences·2025
Same author

Innovative logic "AND" gate gene circuits for bladder cancer treatment: preclinical study.

International journal of surgery (London, England)·2025

Related Experiment Video

Updated: May 23, 2026

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

MARRVEL-MCP: An agentic interface for Mendelian disease discovery via tool-augmented context engineering.

Zachary Everton1, Jorge Botas1, Seon Young Kim2

  • 1Quantitative & Computational Biosciences Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.

American Journal of Human Genetics
|May 21, 2026
PubMed
Summary

MARRVEL-MCP simplifies rare disease variant interpretation by using natural language interfaces for large language models (LLMs). This approach enhances LLM performance, even for smaller models, by providing structured access to genomic tools and databases.

Keywords:
AI-assisted geneticsMARRVELMARRVEL-MCPMendelian disease discoveryfunctional annotationgenomic data integrationlarge language modelsnatural-language query systemsphenotype-to-gene mappingvariant interpretation

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

In Vivo Modeling of the Morbid Human Genome using Danio rerio
12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Related Experiment Videos

Last Updated: May 23, 2026

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

In Vivo Modeling of the Morbid Human Genome using Danio rerio
12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Area of Science:

  • Genomics
  • Bioinformatics
  • Artificial Intelligence in Medicine

Background:

  • Variant interpretation for rare diseases is complex, requiring expertise across multiple genomic databases.
  • Existing tools like MARRVEL have usability barriers due to strict input formats and heterogeneous outputs.
  • This complexity poses challenges for both non-experts and specialists, increasing cognitive load.

Purpose of the Study:

  • To develop MARRVEL-MCP, a natural-language interface for large language models (LLMs) to automate end-to-end variant interpretation.
  • To demonstrate the effectiveness of tool-augmented context engineering in enhancing LLM capabilities for genomics.
  • To improve the accessibility and efficiency of rare disease variant analysis.

Main Methods:

  • Developed MARRVEL-MCP, integrating LLMs with 44 diverse genomic tools via structured function interfaces.
  • Enabled LLMs to perform named-entity recognition, identifier normalization, and multi-database synthesis from clinical queries.
  • Utilized tool-augmented context engineering to guide LLM decision-making without hard-coded workflows.

Main Results:

  • Lightweight LLMs (3B-20B parameters) equipped with MARRVEL-MCP matched or exceeded the performance of larger models without tool access on 100 expert-curated questions.
  • A 20B-parameter model achieved a 94% success rate with MARRVEL-MCP, significantly outperforming the 41% success rate without it.
  • Demonstrated that contextual guidance can compensate for limited model capacity in complex genomic tasks.

Conclusions:

  • MARRVEL-MCP significantly enhances LLM performance in variant interpretation through structured tool access and context engineering.
  • Context engineering is a fundamental principle for advancing biomedical AI and integrating LLMs with genomic resources.
  • This approach supports scalable and more accessible rare disease diagnosis and research.