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Rapid high-resolution typing of Human Leukocyte Antigen genes by nanopore sequencing for transplantation

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI142919-01
Agency Tracking Number: R41AI142919
Amount: $284,282.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA18-575
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2018-12-03
Award End Date (Contract End Date): 2020-11-30
Small Business Information
4320 FOREST PARK AVE. STE 304, Saint Louis, MO, 63108-2979
DUNS: 080743379
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 CHANG LIU
 (503) 709-1055
 cliu@path.wustl.edu
Business Contact
 VICTORIA SWAMIDASS
Phone: (314) 808-5385
Email: victoriagrace@gmail.com
Research Institution
 WASHINGTON UNIVERSITY
 CAMPUS BOX 1054
SAINT LOUIS, MO, 63130-4862
 Nonprofit college or university
Abstract
ABSTRACT Human leukocyte antigenHLAtyping is an essential laboratory test to evaluate the donor recipient compatibility before life saving transplantationsInaloneHLA typing of donors and recipients guided overorgan and stem cell transplantations in the United StatesExisting high resolution HLA typing methods require a turnaround time of days to weeksThere has been an unmet clinical need for a rapidhighresolution HLA typing assay to accelerate donor selection and organ allocation at increased precisionWe propose to develop a kit with bundled software to enable rapidhigh resolution HLA typing by nanopore sequencingThe MinION device by Oxford Nanopore Technologies generates long sequence reads by passing DNA through nanopores while recording the current change in real timeIt is an open platform that supports the development of rapid molecular assaysalthough the high error ratehas hindered its broad application in human genetic testingThe product to be developed will overcome this hurdle to enable MinIONbased high resolution HLA typingThe long term goal of this project is to improve transplant outcomes and further our understanding of transplant immunology through this diagnostic innovationPreviouslyour research team created the ATHLON bioinformatics pipeline and successfully typed the class I HLA genes at the key exon level using reads from the MinION deviceBased on this workwe hypothesize that the ATHLON approach can be adapted to the typing of class II HLA genes by MinION sequencingand the class I and II typing resolution can be increased by considering regions beyond key exonsIn this Phase I studywe aim to demonstrate accurate class II HLA typing by MinION sequencing because a successful HLA typing product must be able to type both class I and II HLA genesWe also aim to demonstrate accurate class I and II HLA typing at a resolution beyond key exons by MinION sequencing within a graphical user interfaceUpon meeting the Phase I milestonesthe Phase II project will focus on streamlining the workflow to meet anhour turnaround timeestablishing quality metrics in the softwareand performing a multicenter validation study to establish the robustness of the productThe proposed HLA typing product will shift the paradigms in the field of HLA diagnostics with a broad appeal to histocompatibility laboratories of different sizesWith a near zero capital investment and a significant saving of hands on timewe expect quick and widespread adoption of this technology in routine clinical HLA typing PUBLIC HEALTH RELEVANCE The objective of this STTR is to deliver a new product that allows rapidhigh resolution typing of tissue antigens by nanopore sequencing to better support organ and stem cell transplantationOverlifesaving transplantations are performed in the United States annuallyand there is an unmet clinical need for faster and more precise tissue typing to expedite organ allocation and inform decision makingOur solution is expected to shorten the turnaround time from weeks days to hoursimprove the resolution of tissue typingand achieve greater cost effectiveness at the same time

* Information listed above is at the time of submission. *

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