Mosquitoes are vectors of numerous infectious diseases. To foster the development of advanced genome- based strategies for vector control, over thirty species have been sequenced and their genomes made publically available through the NIAID funded Bioinformatics Resource Center (BRC) VectorBase. The genome assembly of Culex quinquefasciatus, the major vector of the lymphatic filariasis worm and encephalitis viruses, however remains the most highly fragmented of the major mosquitoes with only 13% of its genome placed onto chromosomes. The lack of a high-quality, chromosome-based genome assembly for Cx. quinquefasciatus remains a substantial impediment to further progress in Culex biology and vector comparative genomics. Using PacBio sequencing, for which we have already assembled two Anopheles genomes de novo, we will reassemble Cx. quinquefasciatus and produce a significantly more contiguous assembly aided by both novel computational innovations and traditional physical mapping. The total number of scaffolds (pieces, also called supercontigs) will be reduced from 3171 to at most ~1750. In addition, this increase in assembly continuity will greatly augment the current cytogenetic map for Cx. quinquefasciatus and help anchor the majority of the genomic scaffolds (old, new or hybrid) to chromosomes. Although the primary goal of this R21 proposal is to significantly improve the genome assembly for Cx. quinquefasciatus, we undertake it with the long-term goal of piloting the sequencing and bioinformatics required to improve other important vectors (e.g., ongoing sandfly and black fly community efforts).
The specific aims for this project are to: 1) improve the quality of the Cx. quinquefasciatus genome assembly through PacBio sequencing; 2) augment and improve this assembly using multicolor fluorescent in situ hybridization; and 3) innovate assembly improvement and comparison within and across mosquitoes. The availability of a high quality genome assembly for Cx. quinquefasciatus through VectorBase will greatly enhance research in vector biology.

Public Health Relevance

The southern house mosquito, Culex quinquefasciatus, is a principal vector of lymphatic filariasis worms and encephalitis viruses, including West Nile virus. The current genome assembly for this mosquito is highly fragmented and as such is a major impediment to further progress in Culex biology and comparative genomics. This project will significantly improve the genome of this important vector by new third-generation sequencing, novel genome improvement and alignment algorithms to better enable comparisons within and across mosquitoes, and integrated physical mapping efforts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI123967-01
Application #
9092877
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-02-15
Project End
2018-01-31
Budget Start
2016-02-15
Budget End
2017-01-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Notre Dame
Department
Biostatistics & Other Math Sci
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556
Choudhury, Olivia; Chakrabarty, Ankush; Emrich, Scott J (2018) HECIL: A Hybrid Error Correction Algorithm for Long Reads with Iterative Learning. Sci Rep 8:9936
Zhu, Shenglong; Chen, Danny Z; Emrich, Scott J (2017) Single molecule sequencing-guided scaffolding and correction of draft assemblies. BMC Genomics 18:879