Dates of HIV infection can be estimated for seroprevalent patients by coalescent analysis of serial next-generation sequencing data

Poon, Art F. Y.; McGovern, Rachel A.; Mo, Theresa; Knapp, David J.H.F.; Brenner, Bluma G.; Routy, Jean‐Pierre; Wainberg, Mark A.; Harrigan, P. Richard

doi:10.1097/qad.0b013e32834b643c

Cited by 36 publications

(39 citation statements)

References 34 publications

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“…Mostly, this choice was based on prior experience (50) and having an implementation of the model already available. On the other hand, reconstructing the ancestral indel pattern was a particularly challenging step.…”

Section: Discussionmentioning

confidence: 99%

“…There are a myriad of programs available for each step of the reconstruction process, and no widely accepted standard for which to use. The packages in our pipeline were chosen based on a combination of literature recommendations and prior experience (50) and limits on computational resources. A great many packages exist for the first step, multiple sequence alignment (see Table 3.1 in reference 54) for a list).…”

Section: Discussionmentioning

confidence: 99%

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An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

McCloskey

Liang

Harrigan

et al. 2014

J Virol

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A population of human immunodeficiency virus (HIV) within a host often descends from a single transmitted/founder virus. The high mutation rate of HIV, coupled with long delays between infection and diagnosis, make isolating and characterizing this strain a challenge. In theory, ancestral reconstruction could be used to recover this strain from sequences sampled in chronic infection; however, the accuracy of phylogenetic techniques in this context is unknown. To evaluate the accuracy of these methods, we applied ancestral reconstruction to a large panel of published longitudinal clonal and/or single-genome-amplification HIV sequence data sets with at least one intrapatient sequence set sampled within 6 months of infection or seroconversion (n ‫؍‬ 19,486 sequences, median [interquartile range] ‫؍‬ 49 [20 to 86] sequences/set). The consensus of the earliest sequences was used as the best possible estimate of the transmitted/founder. These sequences were compared to ancestral reconstructions from sequences sampled at later time points using both phylogenetic and phylogeny-naive methods. Overall, phylogenetic methods conferred a 16% improvement in reproducing the consensus of early sequences, compared to phylogeny-naive methods. This relative advantage increased with intrapatient sequence diversity (P < 10 ؊5 ) and the time elapsed between the earliest and subsequent samples (P < 10 ؊5 ). However, neither approach performed well for reconstructing ancestral indel variation, especially within indel-rich regions of the HIV genome. Although further improvements are needed, our results indicate that phylogenetic methods for ancestral reconstruction significantly outperform phylogeny-naive alternatives, and we identify experimental conditions and study designs that can enhance accuracy of transmitted/founder virus reconstruction. IMPORTANCEWhen HIV is transmitted into a new host, most of the viruses fail to infect host cells. Consequently, an HIV infection tends to be descended from a single "founder" virus. A priority target for the vaccine research, these transmitted/founder viruses are difficult to isolate since newly infected individuals are often unaware of their status for months or years, by which time the virus population has evolved substantially. Here, we report on the potential use of evolutionary methods to reconstruct the genetic sequence of the transmitted/founder virus from its descendants at later stages of an infection. These methods can recover this ancestral sequence with an overall error rate of about 2.3%-about 15% more information than if we had ignored the evolutionary relationships among viruses. Although there is no substitute for sampling infections at earlier points in time, these methods can provide useful information about the genetic makeup of transmitted/founder HIV.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

McCloskey

Liang

Harrigan

et al. 2014

J Virol

Self Cite

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“…Other studies have focused on the analysis of HIV intra-patient evolution, such as the characterization of transmitted HIV and persistence of minority variants [108], estimation of primary infection dates [109], description of intra-host evolution dynamics during the course of infection with or without antiretroviral treatment [95, 98, 103, 107, 110, 111]. Others have analyzed hypermutation patterns [112], viral evolution in different host compartments [113] or in response to the host immune system [114–116], and simultaneous assessment of replication fitness of different drug resistant variants [117].…”

Section: Applications In General Virologymentioning

confidence: 99%

Deep sequencing: Becoming a critical tool in clinical virology

Quiñones‐Mateu¹,

Ávila²,

Reyes‐Terán³

et al. 2014

Journal of Clinical Virology

115

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Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus.

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“…Using NGS results from specimens obtained at two different time points, a date of infection could be determined that was highly correlated with the estimated time of infection derived using other methods. 10 In addition, evidence of the virus' history, in terms of the imprint from the immune system of previous hosts, is detectable in the viral sequence. 11 One can imagine that as these techniques mature, the association between viruses, inferred by the metadata encoded in viral sequence, could lead to more robust association being established among viral sequences.…”

Section: The Power and Pitfalls Of Hiv Phylogenetics In Public Healthmentioning

confidence: 99%

The Power and Pitfalls of HIV Phylogenetics in Public Health

Brooks

Sandstrom

2013

Can J Public Health

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C lassification of living organisms, and the relationship among species, is one of the most enduring pursuits in human beings' efforts to understand their place in the world. Formalized in the early 18 th century by Carl Linnaeus, the phylogeny, or relationship of plant and animals has historically been based upon morphological features. With the advent of rapid and inexpensive DNA sequencing and the development of bioinformatics tools for comparing the genetic sequences from different organisms, we are now in the era of molecular phylogeny. Molecular characterization of both the relationship between species, and among organisms within the same species, has significant implications for public health.Phylogenetic analysis employs the cumulative similarities and weighted polymorphisms found in collections of sequences to build a graphical representation of genetic relatedness. An illustrative example of how a phylogenetic analysis can be shown to infer relationships is presented in Figure 1. Suppose that viral sequences from seven different infected individuals are aligned on the right. One can easily observe that while all seven viruses are identical at the majority of base-pair positions, single nucleotide differences occurring at two positions allow grouping into three phylogenetically related clusters. Each of these monophyletic clusters is in turn linked through an inferred "most recent common ancestors" at the branch points between clusters. In order to accurately resolve the relative relatedness of sequences under investigation, it is critical that care is taken when selecting a suitable set of background sequences for inclusion in the analysis. Similar to the way in which using cats as a reference for comparing different dogs would highlight only the similarities in all canine breeds, using only distantly related reference sequences may cause investigational sequences to appear more highly related. While the basic methods of comparing genetic sequences and quantifying the certainty of the predicted relationships was developed in the 1960s, with the advent of widely available DNA sequencing, ever more sophisticated methods were developed. In the past few years, powerful desktop computers and freely available bioinformatics programs have allowed phylogenetics to become an important tool in increasing our understanding of the epidemiology of infections. 1Application of phylogenetic tools in the context of epidemiology have led to startling revelations and helped to answer and illuminate previously unanswerable questions. The paradigm of the management of TB changed after the publication of an article in the Lancet in 1999.2 It was traditionally assumed that people with TB disease who had no organisms seen on a sputum smear were relatively non-infectious. In this report, Behr and colleagues used DNA fingerprinting on all of the TB cases in San Francisco between 1991 and 1996, to identify clusters of related infections. Through the use of molecular epidemiology, the authors determined that nearly 20% of all TB ...

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Dates of HIV infection can be estimated for seroprevalent patients by coalescent analysis of serial next-generation sequencing data

Abstract: This application of NGS represents an important advancement, not only because accurate estimates of dates of infection can be derived retrospectively from archived specimens, but also because each analysis is patient-specific and, therefore, robust to variation in rates of HIV evolution.

Cited by 36 publications

References 34 publications

An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

Deep sequencing: Becoming a critical tool in clinical virology

The Power and Pitfalls of HIV Phylogenetics in Public Health

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