Award Abstract # 2027669
RAPID: Deciphering Within-host Diversity and Multi-strain Infections in COVID-19

NSF Org: CCF
Division of Computing and Communication Foundations
Recipient: UNIVERSITY OF ILLINOIS
Initial Amendment Date: May 4, 2020
Latest Amendment Date: May 4, 2020
Award Number: 2027669
Award Instrument: Standard Grant
Program Manager: Mitra Basu
mbasu@nsf.gov
 (703)292-8649
CCF
 Division of Computing and Communication Foundations
CSE
 Directorate for Computer and Information Science and Engineering
Start Date: May 15, 2020
End Date: April 30, 2021 (Estimated)
Total Intended Award Amount: $100,000.00
Total Awarded Amount to Date: $100,000.00
Funds Obligated to Date: FY 2020 = $100,000.00
History of Investigator:
  • Mohammed El-Kebir (Principal Investigator)
    melkebir@illinois.edu
  • Jian Peng (Co-Principal Investigator)
Recipient Sponsored Research Office: University of Illinois at Urbana-Champaign
506 S WRIGHT ST
URBANA
IL  US  61801-3620
(217)333-2187
Sponsor Congressional District: 13
Primary Place of Performance: The Board of Trustees of the University of Illinois
506 S. Wright Street
Urbana
IL  US  61801-2302
Primary Place of Performance
Congressional District:
13
Unique Entity Identifier (UEI): Y8CWNJRCNN91
Parent UEI: V2PHZ2CSCH63
NSF Program(s): COVID-19 Research
Primary Program Source: 010N2021DB R&RA CARES Act DEFC N
Program Reference Code(s): 096Z, 7914, 7931
Program Element Code(s): 158Y00
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.070
Note: This Award includes Coronavirus Aid, Relief, and Economic Security (CARES) Act funding.

ABSTRACT

To facilitate real-time outbreak management and mitigation strategies, there is an urgent need to understand the spread of COVID-19. Researchers reconstruct the evolutionary and transmission history of the virus by applying algorithms to sequencing samples of COVID-19 patients. However, a key challenge is the presence of multiple strains of the virus within hosts, which is overlooked by current algorithms. This RAPID project will improve the nation?s COVID-19 response by developing algorithms to characterize the ongoing evolution and spread of the viral strains that coexist within patients. The developed algorithms will be applicable to future disease outbreaks.

This RAPID project seeks to understand the impact of within-host viral diversity on the current spread of COVID-19. The project will identify the viral strains coexisting in patients through the development of algorithms that deconvolve COVID-19 sequencing samples. Subsequently, the project will assess whether or not such coexisting strains are the result of multiple infection events. Finally, the project will quantify the severity of the identified viral strains through a protein functional analysis of their mutations. Results will be disseminated through an online portal that enable labs and hospitals to upload their sequencing reads and generate annotations and characterizations of COVID-19 viral strains.

In summary, the goal of this research is to understand SARS-CoV-2 by investigating the evolutionary origins of the virus and its genetic variation within host species in order to determine how molecular variation correlates with host range, and to evaluate risk of further disease emergence.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Oh, Chamteut and Sashittal, Palash and Zhou, Aijia and Wang, Leyi and El-Kebir, Mohammed and Nguyen, Thanh H. "Design of SARS-CoV-2 Variant-Specific PCR Assays Considering Regional and Temporal Characteristics" Applied and Environmental Microbiology , v.88 , 2022 https://doi.org/10.1128/aem.02289-21 Citation Details
Sashittal, Palash and El-Kebir, Mohammed "Sampling and summarizing transmission trees with multi-strain infections" Bioinformatics , v.36 , 2020 https://doi.org/10.1093/bioinformatics/btaa438 Citation Details
Sashittal, Palash and Zhang, Chuanyi and Peng, Jian and El-Kebir, Mohammed "Jumper enables discontinuous transcript assembly in coronaviruses" Nature Communications , v.12 , 2021 https://doi.org/10.1038/s41467-021-26944-y Citation Details
Zhang, Chuanyi and Sashittal, Palash and Xiang, Michael and Zhang, Yichi and Kazi, Ayesha and El-Kebir, Mohammed "Accurate Identification of Transcription Regulatory Sequences and Genes in Coronaviruses" Molecular Biology and Evolution , 2022 https://doi.org/10.1093/molbev/msac133 Citation Details

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

To facilitate real-time outbreak management and mitigation strategies, there is an urgent need to understand the spread of COVID-19. Researchers reconstruct the evolutionary and transmission history of the virus by applying algorithms to sequencing samples of COVID-19 patients. However, a key challenge is the presence of multiple variants of the virus within hosts, which is overlooked by current algorithms. This RAPID project sought to improve the nation’s COVID-19 response by developing algorithms to characterize the ongoing evolution and spread of the viral variants that coexist within patients. The developed algorithms will be applicable to future disease outbreaks. Beyond SARS-CoV-2, this project also sought novel algorithms to reconstruct transcriptomes of coronaviruses and identify regulatory sequences within coronavirus genomes.

This RAPID project has supported the development of:

  1. Algorithms and theory to reconstruct multi-strain/multi-variant infections given a timed phylogeny and additional epidemiological data.
     
  2. Pipeline for SARS-CoV-2 sequence analysis. 

  3. Algorithms and theory for reconstruction of coronavirus transcriptomes.
     
  4. Tool for generating SARS-CoV-2 variant-specific primers.

    The tool takes as input GISAID sequences of SARS-CoV-2 viruses from COVID-19 patients from around the world, a set of target sequences, and a lineage of interest. The tool then computes for each input target sequence, as well as combinations of input sequences, the sensitivity and specificity for identifying the lineage of interest as a function of time.

  5. Algorithms and theory to identify core and transcription regulatory sequences of coronavirus genomes.

Last Modified: 09/02/2021
Modified by: Mohammed El-Kebir

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