# Metagenomic shotgun microbial sequencing in post-transplant lymphoproliferative disorders (PTLD-MSMS)

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $641,440

## Abstract

Abstract
Post-transplant lymphoproliferative disorders (PTLDs) remain a feared malignant complication of
transplantation, with high 5-year mortality and morbidity exceeding 50%. About 50-80% of cases are strongly
related to the oncogenic Epstein-Barr virus (EBV), a key pathogenic driver. Many knowledge gaps exist in
PTLD. Several prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics,
including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting an
additional role for EBV genome variants or other viral etiologies. However, the precision medicine tools for
determining if a viral genome variant is pathogenic are very limited compared to human genome variants.
Further, the etiological agent in EBV-negative PTLD is unknown. Using novel recently developed cutting-edge
technologies, we can extract viral nucleic acids from formalin-fixed, paraffin-embedded archived PTLD tissues
or plasma and sequence multiple viruses simultaneously in unbiased fashion, using metagenomic shotgun
sequencing (MSS) and ViroCap™. Based on our preliminary data, we propose a precision medicine
translational genomics project to address the following specific aims and close the cited knowledge gaps: 1)
Validate our novel observation that PTLD tissue positivity by MSS for anellovirus (and confirmed by other
techniques) serves as a biomarker for higher transplant recipient mortality after the diagnosis of PTLD; 2)
Determine the role of other oncogenic viruses in EBV-negative PTLD by unbiased MSS of multiple viral
groupings, confirmed by other techniques; 3) Develop the necessary computational, algorithmic and software
analytic tools required to then determine association of EBV genome variants with worse presentations or
outcomes in PTLD. To achieve these aims, we will retrospectively collect PTLD tissues and prospectively
collect PTLD tissues/plasma from: 1) cases at Washington University that have occurred after 2015; 2) three
USA sites with large transplant programs and existing PTLD collections (Universities of Pennsylvania,
Pittsburgh and Stanford; 3) a French national-level PTLD registry that already has extensive clinical data and
can obtain archived tissues. In this proposed sample size of adequately powered 630 PTLD cases, we will: a)
acquire tissue scrolls from the PTLD samples and transport to Washington University; b) extract the microbial
DNA and RNA; c) perform metagenomic shotgun sequencing; and d) validate our novel associations to the
clinical data, imported from each of the sites, into an already constructed RedCap database. Our team includes
specialists in transplantation, hematopathology, infectious diseases, oncology, genomics, data management
and statistics. Our preliminary data, collaborators and local resources are exceptional to accomplish these
goals. This study will additionally create the largest-to-date repository of combined PTLD tissue, extracted
nucleic acids, and well-anno...

## Key facts

- **NIH application ID:** 10180895
- **Project number:** 5R01AI142135-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Vikas R. Dharnidharka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $641,440
- **Award type:** 5
- **Project period:** 2019-06-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180895

## Citation

> US National Institutes of Health, RePORTER application 10180895, Metagenomic shotgun microbial sequencing in post-transplant lymphoproliferative disorders (PTLD-MSMS) (5R01AI142135-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180895. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*