# Micropublications for Automating Genome Sequence Variant Interpretation from Medical Literature

> **NIH NIH R44** · GENOMENON, INC. · 2022 · $855,024

## Abstract

PROJECT SUMMARY
Accurate and efficient interpretation of genomic variants for clinical decision making is predicated on ready
access to and extraction of information from the medical literature. The sheer number of potentially relevant
articles that must be examined during this process poses a significant challenge in ensuring the accuracy and
reproducibility of clinical interpretation as it is time-consuming, error-prone, and highly user-dependent. To this
end, we have developed the Mastermind Genomic Search Engine - a commercial database that automatically
organizes disease, gene and variant information from the medical literature by systematically indexing millions
of scientific articles. Mastermind is used by over 9,100 variant scientists in more than 100 different countries to
more quickly interpret genetic variants in clinical settings. In Phase I of this project, we developed and tested a
micropublication platform within Mastermind that assembles literature curation along with population frequency
data, computational predictions of pathogenicity, and automated ACMG/AMP classifications that improves the
speed of variant interpretation by more than 70% and increases the sensitivity of these results by 2-20x. The
present proposal seeks to build on the success of Phase I by 1) integrating the micropublication platform into
Mastermind with migration of collaborative features for community-based evaluation of variant interpretations; 2)
optimizing and improving automated variant interpretation/prioritization of articles and implementing a rigorous
quality assurance process; and 3) using these improvements to curate all evidence in all variants in all genes
comprising the entire human genome, beginning with the clinical exome. Integration of the pre-curated genome
data in the micropublication platform will result in Mastermind Enterprise, allowing for immediate and accurate
genome-wide variant interpretations with collaborative curation in real-time at the point of interaction with source
material (i.e. individual references). This work will mitigate reproducibility challenges plaguing other large-scale
crowd-sourced projects, including those undertaken by groups like NIH’s ClinVar and QIAGEN’s HGMD. In
addition, our novel approach will not suffer from poor sensitivity as it relies on a comprehensive source of medical
literature pre-annotated based on genetic content. This work will permit dramatic scaling of variant interpretation
activities and allow for complete and accurate curation of the entire human genome within 2 years – a feat that
could not be completed utilizing current manual methods for variant interpretation. Mastermind Enterprise will be
revolutionary in the genomics industry and will represent a natural next step to build on the achievements
provided by the Human Genome Project and the reduced cost of next-generation sequencing. It will substantially
improve diagnostic rates and accuracy in the clinic, especially in rare disease,...

## Key facts

- **NIH application ID:** 10491767
- **Project number:** 5R44HG010446-03
- **Recipient organization:** GENOMENON, INC.
- **Principal Investigator:** Mark Julin Kiel
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $855,024
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491767

## Citation

> US National Institutes of Health, RePORTER application 10491767, Micropublications for Automating Genome Sequence Variant Interpretation from Medical Literature (5R44HG010446-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10491767. Licensed CC0.

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