# Bioinformatics Core

> **NIH NIH P50** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $399,347

## Abstract

Project Summary – Bioinformatics Core
The objective of this Bioinformatics Core is to support statistical and bioinformatics analyses to
study the effects of osteoporosis anabolic therapies (romosozumab, a sclerostin inhibitor, Scl-
Ab) on osteoblast progenitors as well as osteocytes in clinical and pre-clinical studies with
anabolic therapies. A short anabolic treatment window from Scl-Ab has been reported; in
contrast to teriparatide (PTH) that has a longer anabolic window. This Bioinformatics Core will
serve as the critical foundation for the research projects by analyzing cross-species data from
single cell RNA-seq (scRNA-seq) and bulk RNA-seq using innovative techniques and approaches.
The capabilities of the Bioinformatics Core will be enhanced by being able to leverage existing
datasets of whole genome sequencing in tens thousands of human samples; and osteocyte
gene expression signatures and deeply skeletal phenotyping from a unique mouse knockout
dataset from our collaborators. To support Project #1, Project #2 as well as pilot projects, the
Bioinformatics Core will provide statistical design, computational analysis, data quality control
and management support as well as accessing to other external human genetics and
bioinformatics data and resource. Specifically, in Aim 1, the Bioinformatics Core seeks to build a
synergistic data management, data analytical and bioinformatics pipelines over cloud
computing environment which allows interaction within investigators through data collection,
data analyses, information sharing and data interpretation. In Aim 2, the Core will provide
statistical and bioinformatics analyses for scRNA-seq and bulk RNA-seq generated from clinical
and pre-clinical studies to identify osteoblast precursor cell clusters over time with either Scl-Ab
or PTH treatments; osteoblast lineage tracing; osteoblast progenitors and osteocytes gene
expression patterns; and co-expression pattern over time. In addition, cross-species integrating
analysis will be conducted to identify homologous and divergent cell types between human and
mice. In Aim 3, we will prioritize genes regulating bone formation and Identify molecular
signatures affecting treatment effect via human gene expression (in bone biopsies) and genetic
variation associated with bone phenotypes (BMD, HR-PQCT derived bone structure, fracture) in
large-scale whole genome sequenced studies. In Aim 4, To further characterize skeletal function
and phenotypes of the genes identified from project# and project#2 transcriptome analyses, we
will utilize the existing KO mice deep phenotyping data; and generate a new KO mice strain.
Ultimately, these merged analyses will generate powerfully informed, novel hypotheses
regarding bone stem cell biology and responses to bone anabolic agents.

## Key facts

- **NIH application ID:** 10757743
- **Project number:** 5P50AR080596-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Yi-Hsiang Hsu
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,347
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757743

## Citation

> US National Institutes of Health, RePORTER application 10757743, Bioinformatics Core (5P50AR080596-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10757743. Licensed CC0.

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