# Sequencing and Bioinformatics

> **NIH NIH U54** · SEATTLE CHILDREN'S HOSPITAL · 2022 · $216,225

## Abstract

ABSTRACT, CORE 4
Next-Generation Sequencing is an essential and fundamental approach in molecular virology. In vitro, it can
capture and characterize protein-nucleic interactions and RNA structure. In cell culture and in clinical settings, it
can measure rates of viral polymerase error, viral response to small molecule inhibitors or changes in host gene
expression. NGS can chart viral evolution, patterns of genome conservation, characterize origins of drug
resistance and discover new viruses. As such, NGS has been transformative in our ability to study virus diversity
and evolution and is still a burgeoning field. The Sequencing Core comprises a group of experts with experience
with the implementation of the wide range of approaches in terms of molecular biology, experimental design,
and downstream computational analyses. We will provide expert support and resources to provide Next-
Generation Sequencing and downstream computational analyses to the B-HIVE Research Projects.
Importantly, a key focus of the core will be to develop and apply approaches that go beyond what is accessible
via commercial and university core facilities. We will provide and develop state-of-the-art technologies in close
collaboration with the Research Projects that will help provide unique insights into HIV biology and evolution,
whilst also providing novel platforms for deployments in other viral systems.
A central focus of the B-HIVE is to understand the molecular mechanisms governing HIV entry, integration,
particle assembly, and egress. Each of these processes involve profiling the viral and host nucleic acids during
the viral lifecycle. The sequencing core will support the entire B-HIVE reflecting stages throughout the viral
replication cycle. We will develop single-cell sequencing approaches, leveraging our extensive expertise in this
area, to characterize the effects of integration site location, chromatin structure, HIV mutations, and exposure to
latency reversing agents (LRAs) on proviral expression. We will apply and advance long-read sequencing
technologies using the Oxford Nanopore Technologies MinION platform for both host transcriptomics and full-
length HIV genome sequencing to characterize host and virus splicing. We will develop and implement novel
approaches in virus genomics to characterize virus sequence diversity in both clinical and experimental settings
in support of the main Research Projects. The Sequencing Core has extensive experience developing, deploying
and maintaining new computational software and sequencing databases. These will provide an important
resource to the B-HIVE centers, as well as allow the rapid dissemination and sharing of capabilities with the
broader HIV and virus research community. Finally, we will provide training in each of our respective platforms
and technologies in view of disseminating these skills throughout the B-HIVE and to support the development
and progression of trainees working with the B-HIVE and its collabo...

## Key facts

- **NIH application ID:** 10508449
- **Project number:** 1U54AI170855-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Andrew Laurence Routh
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,225
- **Award type:** 1
- **Project period:** 2022-06-22 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508449

## Citation

> US National Institutes of Health, RePORTER application 10508449, Sequencing and Bioinformatics (1U54AI170855-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10508449. Licensed CC0.

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