Order preservation of expected information content using Unscented Transform approximation of multivariate prior distributions in HIV 2-LTR experiment design

Abraham, George; Jagarapu, Aditya; Cannon, LaMont; Zurakowski, Ryan

doi:10.1109/cdc.2016.7799129

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…It has been shown the sample schedule order is preserved when KLD is calculated using the simplified method in lieu of integrating over the entire distribution [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

HIV 2-LTR experiment design optimization

et al. 2018

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Clinical trials are necessary in order to develop treatments for diseases; however, they can often be costly, time consuming, and demanding to the patients. This paper summarizes several common methods used for optimal design that can be used to address these issues. In addition, we introduce a novel method for optimizing experiment designs applied to HIV 2-LTR clinical trials. Our method employs Bayesian techniques to optimize the experiment outcome by maximizing the Expected Kullback-Leibler Divergence (EKLD) between the a priori knowledge of system parameters before the experiment and the a posteriori knowledge of the system parameters after the experiment. We show that our method is robust and performs equally well if not better than traditional optimal experiment design techniques.

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“…It has been shown the sample schedule order is preserved when KLD is calculated using the simplified method in lieu of integrating over the entire distribution [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

HIV 2-LTR experiment design optimization

et al. 2018

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“…However, do to Institutional Review Board (IRB) limits on the amount of blood that can be drawn during a clinical trial, as well as costs associated with acquiring patient samples, only a few samples can be taken to fit the model [1], [21], [22]. There is also inherent noise in the quantification of the HIV DNA via PCR assay.…”

Section: Introductionmentioning

confidence: 99%

Implications of measurement assay type in design of HIV experiments

Cannon

Jagarapu

Vargas-García

et al. 2017

2017 IEEE 56th Annual Conference on Decision and Control (CDC)

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Time series measurements of circular viral episome (2-LTR) concentrations enable indirect quantification of persistent low-level Human Immunodeficiency Virus (HIV) replication in patients on Integrase-Inhibitor intensified Combined Antiretroviral Therapy (cART). In order to determine the magnitude of these low level infection events, blood has to be drawn from a patients at a frequency and volume that is strictly regulated by the Institutional Review Board (IRB). Once the blood is drawn, the 2-LTR concentration is determined by quantifying the amount of HIV DNA present in the sample via a PCR (Polymerase Chain Reaction) assay. Real time quantitative Polymerase Chain Reaction (qPCR) is a widely used method of performing PCR; however, a newer droplet digital Polymerase Chain Reaction (ddPCR) method has been shown to provide more accurate quantification of DNA. Using a validated model of HIV viral replication, this paper demonstrates the importance of considering DNA quantification assay type when optimizing experiment design conditions. Experiments are optimized using a Genetic Algorithm (GA) to locate a family of suboptimal sample schedules which yield the highest fitness. Fitness is defined as the expected information gained in the experiment, measured by the Kullback-Leibler Divergence (KLD) between the prior and posterior distributions of the model parameters. We compare the information content of the optimized schedules to uniform schedules as well as two clinical schedules implemented by researchers at UCSF and the University of Melbourne. This work shows that there is a significantly greater gain information in experiments using a ddPCR assay vs. a qPCR assay and that certain experiment design considerations should be taken when using either assay.

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Insights into the Coordination Behavior of Methyl-Substituted Phosphinic Acids with Actinides

et al. 2022

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The electronic structure and complexation behavior of methylsubstituted phosphinic acids with U(VI) and Pu(IV) were explored by applying quantum chemical methods. In contrast to Ingold's classification, our results indicate that the methyl group is electron-withdrawing, reducing the phosphoryl group electron density in substituted phosphinic acids. The magnitude of the computed complexation energy values increases along with the series, PA → MPA → DMPA, and MP → MMP → MDMP, implying an increasing complexation tendency upon methyl group substitution for both U(VI) and Pu(IV) complexes. One of the nitrate groups in UO 2 (NO 3 ) 2 •2L complexes (L = PA, MPA, and DMPA) is in monodentate coordination mode due to the additional stability gained from O 2 N−O•••H hydrogen bonding interactions with the acidic H atoms of respective ligands. The calculation indicates marginally stronger metal−ligand interactions in Pu(IV) complexes compared to that in U(VI), which is supported by the computed complexation energies, M−O P bond lengths, ν(P�O), the extent of metal−ligand charge transfer, and properties of M−O P bond critical points. The energy landscape of substituted phosphinic acid ligands is further analyzed within the framework of the activation strain model to explain the energetic preference of certain conformers.

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Order preservation of expected information content using Unscented Transform approximation of multivariate prior distributions in HIV 2-LTR experiment design

Cited by 3 publications

References 28 publications

HIV 2-LTR experiment design optimization

HIV 2-LTR experiment design optimization

Implications of measurement assay type in design of HIV experiments

Insights into the Coordination Behavior of Methyl-Substituted Phosphinic Acids with Actinides

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