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Article ; Online: Incorporating metadata in HIV transmission network reconstruction

Sepideh Mazrouee / Susan J Little / Joel O Wertheim

PLoS Computational Biology, Vol 17, Iss 9, p e

A machine learning feasibility assessment.

2021 Volume 1009336

Abstract: HIV molecular epidemiology estimates the transmission patterns from clustering genetically similar viruses. The process involves connecting genetically similar genotyped viral sequences in the network implying epidemiological transmissions. This ... ...

Abstract	HIV molecular epidemiology estimates the transmission patterns from clustering genetically similar viruses. The process involves connecting genetically similar genotyped viral sequences in the network implying epidemiological transmissions. This technique relies on genotype data which is collected only from HIV diagnosed and in-care populations and leaves many persons with HIV (PWH) who have no access to consistent care out of the tracking process. We use machine learning algorithms to learn the non-linear correlation patterns between patient metadata and transmissions between HIV-positive cases. This enables us to expand the transmission network reconstruction beyond the molecular network. We employed multiple commonly used supervised classification algorithms to analyze the San Diego Primary Infection Resource Consortium (PIRC) cohort dataset, consisting of genotypes and nearly 80 additional non-genetic features. First, we trained classification models to determine genetically unrelated individuals from related ones. Our results show that random forest and decision tree achieved over 80% in accuracy, precision, recall, and F1-score by only using a subset of meta-features including age, birth sex, sexual orientation, race, transmission category, estimated date of infection, and first viral load date besides genetic data. Additionally, both algorithms achieved approximately 80% sensitivity and specificity. The Area Under Curve (AUC) is reported 97% and 94% for random forest and decision tree classifiers respectively. Next, we extended the models to identify clusters of similar viral sequences. Support vector machine demonstrated one order of magnitude improvement in accuracy of assigning the sequences to the correct cluster compared to dummy uniform random classifier. These results confirm that metadata carries important information about the dynamics of HIV transmission as embedded in transmission clusters. Hence, novel computational approaches are needed to apply the non-trivial knowledge collected from inter-individual genetic information to metadata from PWH in order to expand the estimated transmissions. We note that feature extraction alone will not be effective in identifying patterns of transmission and will result in random clustering of the data, but its utilization in conjunction with genetic data and the right algorithm can contribute to the expansion of the reconstructed network beyond individuals with genetic data.
Keywords	Biology (General) ; QH301-705.5
Subject code	006
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The re-emergence of H1N1 influenza virus in 1977

Joel O Wertheim

PLoS ONE, Vol 5, Iss 6, p e

a cautionary tale for estimating divergence times using biologically unrealistic sampling dates.

2010 Volume 11184

Abstract: In 1977, H1N1 influenza A virus reappeared after a 20-year absence. Genetic analysis indicated that this strain was missing decades of nucleotide sequence evolution, suggesting an accidental release of a frozen laboratory strain into the general ... ...

Abstract	In 1977, H1N1 influenza A virus reappeared after a 20-year absence. Genetic analysis indicated that this strain was missing decades of nucleotide sequence evolution, suggesting an accidental release of a frozen laboratory strain into the general population. Recently, this strain and its descendants were included in an analysis attempting to date the origin of pandemic influenza virus without accounting for the missing decades of evolution. Here, we investigated the effect of using viral isolates with biologically unrealistic sampling dates on estimates of divergence dates. Not accounting for missing sequence evolution produced biased results and increased the variance of date estimates of the most recent common ancestor of the re-emergent lineages and across the entire phylogeny. Reanalysis of the H1N1 sequences excluding isolates with unrealistic sampling dates indicates that the 1977 re-emergent lineage was circulating for approximately one year before detection, making it difficult to determine the geographic source of reintroduction. We suggest that a new method is needed to account for viral isolates with unrealistic sampling dates.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2010-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of molecular sequence data completeness on HIV cluster detection and a network science approach to enhance detection

Sepideh Mazrouee / Camden J. Hallmark / Ricardo Mora / Natascha Del Vecchio / Rocio Carrasco Hernandez / Michelle Carr / Marlene McNeese / Kayo Fujimoto / Joel O. Wertheim

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the ...

Abstract	Abstract Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the reconstructed molecular transmission network. We analyzed viral sequence data available from ~ 13,000 individuals with diagnosed HIV (2012–2019) from Houston Health Department surveillance data with 53% completeness (n = 6852 individuals with sequences). We extracted random subsamples and compared the resulting reconstructed networks versus the full-size network. Increasing simulated completeness was associated with an increase in the number of detected clusters. We also subsampled based on the network node influence in the transmission of the virus where we measured Expected Force (ExF) for each node in the network. We simulated the removal of nodes with the highest and then lowest ExF from the full dataset and discovered that 4.7% and 60% of priority clusters were detected respectively. These results highlight the non-uniform impact of capturing high influence nodes in identifying transmission clusters. Although increasing sequence reporting completeness is the way to fully detect HIV transmission patterns, reaching high completeness has remained challenging in the real world. Hence, we suggest taking a network science approach to enhance performance of molecular cluster detection, augmented by node influence information.
Keywords	Medicine ; R ; Science ; Q
Subject code	000
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishing a framework towards monitoring HCV microelimination among men who have sex with men living with HIV in Germany

Lara K Marquez / Patrick Ingiliz / Christoph Boesecke / Ivanka Krznaric / Knud Schewe / Thomas Lutz / Stefan Mauss / Stefan Christensen / Jürgen K Rockstroh / Sonia Jain / Feng He / Joel O Wertheim / Natasha K Martin

PLoS ONE, Vol 17, Iss 5, p e

A modeling analysis.

2022 Volume 0267853

Abstract: Background Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to ... ...

Abstract	Background Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. Methods To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. Results Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. Conclusions HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishing a framework towards monitoring HCV microelimination among men who have sex with men living with HIV in Germany

Lara K. Marquez / Patrick Ingiliz / Christoph Boesecke / Ivanka Krznaric / Knud Schewe / Thomas Lutz / Stefan Mauss / Stefan Christensen / Jürgen K. Rockstroh / Sonia Jain / Feng He / Joel O. Wertheim / Natasha K. Martin

PLoS ONE, Vol 17, Iss

A modeling analysis

2022 Volume 5

Abstract	Background Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. Methods To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. Results Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015–2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. Conclusions HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dating the age of the SIV lineages that gave rise to HIV-1 and HIV-2.

Joel O Wertheim / Michael Worobey

PLoS Computational Biology, Vol 5, Iss 5, p e

2009 Volume 1000377

Abstract: Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV) and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates ... ...

Abstract	Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV) and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266-1685), and the date in sooty mangabeys is estimated to be 1809 (1729-1875). Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948-1977). Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.
Keywords	Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2009-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes.

Joel O Wertheim / Michael Worobey

PLoS Pathogens, Vol 3, Iss 7, p e

2007 Volume 95

Abstract: While the circumstances surrounding the origin and spread of HIV are becoming clearer, the particulars of the origin of simian immunodeficiency virus (SIV) are still unknown. Specifically, the age of SIV, whether it is an ancient or recent infection, has ...

Abstract	While the circumstances surrounding the origin and spread of HIV are becoming clearer, the particulars of the origin of simian immunodeficiency virus (SIV) are still unknown. Specifically, the age of SIV, whether it is an ancient or recent infection, has not been resolved. Although many instances of cross-species transmission of SIV have been documented, the similarity between the African green monkey (AGM) and SIVagm phylogenies has long been held as suggestive of ancient codivergence between SIVs and their primate hosts. Here, we present well-resolved phylogenies based on full-length AGM mitochondrial genomes and seven previously published SIVagm genomes; these allowed us to perform the first rigorous phylogenetic test to our knowledge of the hypothesis that SIVagm codiverged with the AGMs. Using the Shimodaira-Hasegawa test, we show that the AGM mitochondrial genomes and SIVagm did not evolve along the same topology. Furthermore, we demonstrate that the SIVagm topology can be explained by a pattern of west-to-east transmission of the virus across existing AGM geographic ranges. Using a relaxed molecular clock, we also provide a date for the most recent common ancestor of the AGMs at approximately 3 million years ago. This study substantially weakens the theory of ancient SIV infection followed by codivergence with its primate hosts.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	930
Language	English
Publishing date	2007-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Kayo Fujimoto / Justin Bahl / Joel O. Wertheim / Natascha Del Vecchio / Joseph T. Hicks / Lambodhar Damodaran / Camden J. Hallmark / Richa Lavingia / Ricardo Mora / Michelle Carr / Biru Yang / John A. Schneider / Lu-Yu Hwang / Marlene McNeese

Scientific Reports, Vol 11, Iss 1, Pp 1-

Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE: HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context

2021 Volume 2

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE

Scientific Reports, Vol 11, Iss 1, Pp 1-

HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context

2021 Volume 10

Abstract: Abstract This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, ...

Abstract	Abstract This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, TX, the largest city in the Southern United States. Using 6332 HIV-1 pol sequences from persons newly diagnosed with HIV during the period 2010–2018, we reconstructed HIV-1 transmission clusters, using the HIV-TRAnsmission Cluster Engine (HIV-TRACE); inferred demographic and risk parameters on HIV-1 transmission dynamics by jointly estimating viral transmission rates across racial/ethnic, age, and transmission risk groups; and modeled the degree of network connectivity by using generalized estimating equations (GEE). Our results indicate that Hispanics/Latinos are most vulnerable to the structure of transmission clusters and serve as a bridge population, acting as recipients of transmissions from Whites (3.0 state changes/year) and from Blacks (2.6 state changes/year) as well as sources of transmissions to Whites (1.8 state changes/year) and to Blacks (1.2 state changes/year). There were high rates of transmission and high network connectivity between younger and older Hispanics/Latinos as well as between younger and older Blacks. Prevention and intervention efforts are needed for transmission clusters that involve younger racial/ethnic minorities, in particular Hispanic/Latino youth, to reduce onward transmission of HIV in Houston.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Natural selection favoring more transmissible HIV detected in United States molecular transmission network

Joel O. Wertheim / Alexandra M. Oster / William M. Switzer / Chenhua Zhang / Nivedha Panneer / Ellsworth Campbell / Neeraja Saduvala / Jeffrey A. Johnson / Walid Heneine

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract: Here, the authors use a molecular epidemiological approach to investigate the frequency and intensity of clustering of HIV with different set-point viral loads and find that frequently transmitted strains in genetic transmission clusters have ... ...

Abstract	Here, the authors use a molecular epidemiological approach to investigate the frequency and intensity of clustering of HIV with different set-point viral loads and find that frequently transmitted strains in genetic transmission clusters have significantly higher viral loads than nonclustered viruses.
Keywords	Science ; Q
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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