Title

Towards Personalized Medicine: An Improved De Novo Assembly Procedure for Early Detection of Drug Resistant HIV Minor Quasispecies in Patient Samples

Authors

Cindy Huang^1,2, Vichetra Sam^1,3, Sophie Du^1,3, Tuan Le¹, Anthony Fletcher¹, William Lau¹, Kathleen Meyer^1,3, Esther Asaki^1,3, Da Wei Huang¹*, Calvin Johnson¹*

Affiliation

¹Center for Information Technology, National Institutes of Health, Bethesda, Maryland 10891;

²Thomas Wootton High School, Rockville, Maryland 20850; 3CSRA, Falls Church, VA 22042;

Email

huangdawei@mail.nih.gov; johnson@mail.nih.gov

Article Type

Software Model

Date

Received August 30, 2018; Revised September 17, 2018; Accepted September 17, 2018; Published September 18, 2018

The third-generation sequencing technology, PacBio, has shown an ability to sequence the HIV virus amplicons in their full length. The long read of PaBio offers a distinct advantage to comprehensively understand the virus evolution complexity at quasispecies level (i.e. maintaining linkage information of variants) comparing to the short reads from Illumina shotgun sequencing. However, due to the high noise nature of the PacBio reads, it is still a challenge to build accurate contigs at high sensitivity. Most of previously developed NGS assembly tools work with the assumption that the input reads are fairly accurate, which is largely true for the data derived from Sanger or Illumina technologies. When applying these tools on PacBio high-noise reads, they are largely driven by noise rather than true signal eventually leading to poor results in most cases. In this study, we propose the de novo assembly procedure, which comprises a positive focused strategy, and linkage-frequency noise reduction so that it is more suitable for PacBio high-noise reads. We further tested the unique de novo assembly procedure on HIV PacBio benchmark data and clinical samples, which accurately assembled dominant and minor populations of HIV quasispecies as expected. The improved de novo assembly procedure shows potential ability to promote PacBio technology in the field of HIV drug-resistance clinical detection, as well as in broad HIV phylogenetic studies.

Keywords

De Novo Assembly, HIV, PacBio, quasispecies

Citation

Huang et al. Bioinformation 14(8): 449-454 (2018)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.