A statistical characterization of consistent patterns of human immunodeficiency virus evolution within infected patients.
Scott Williamson,Steven M. Perry,Carlos Bustamante,Maria E. Orive,Miles N. Stearns,John K. Kelly +5 more
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These analyses statistically confirm that an evolutionary slowdown occurs late in infection, strongly support the immune-relaxation hypothesis, and indicate that the cessation of nonsynonymous evolution is associated with disease progression.Abstract:
Within-patient HIV populations evolve rapidly because of a high mutation rate, short generation time, and strong positive selection pressures. Previous studies have identified "consistent patterns" of viral sequence evolution. Just before HIV infection progresses to AIDS, evolution seems to slow markedly, and the genetic diversity of the viral population drops. This evolutionary slowdown could be caused either by a reduction in the average viral replication rate or because selection pressures weaken with the collapse of the immune system. The former hypothesis (which we denote "cellular exhaustion") predicts a simultaneous reduction in both synonymous and nonsynonymous evolution, whereas the latter hypothesis (denoted "immune relaxation") predicts that only nonsynonymous evolution will slow. In this paper, we present a set of statistical procedures for distinguishing between these alternative hypotheses using DNA sequences sampled over the course of infection. The first component is a new method for estimating evolutionary rates that takes advantage of the temporal information in longitudinal DNA sequence samples. Second, we develop a set of probability models for the analysis of evolutionary rates in HIV populations in vivo. Application of these models to both synonymous and nonsynonymous evolution affords a comparison of the cellular-exhaustion and immune-relaxation hypotheses. We apply the procedures to longitudinal data sets in which sequences of the env gene were sampled over the entire course of infection. Our analyses (1) statistically confirm that an evolutionary slowdown occurs late in infection, (2) strongly support the immune-relaxation hypothesis, and (3) indicate that the cessation of nonsynonymous evolution is associated with disease progression.read more
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Genome-wide patterns of nucleotide polymorphism in domesticated rice
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Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection
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Synonymous Substitution Rates Predict HIV Disease Progression as a Result of Underlying Replication Dynamics
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References
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Bootstrap Methods and Their Application
Anthony C. Davison,David Hinkley +1 more
TL;DR: In this paper, a broad and up-to-date coverage of bootstrap methods, with numerous applied examples, developed in a coherent way with the necessary theoretical basis, is given, along with a disk of purpose-written S-Plus programs for implementing the methods described in the text.
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Forecasting, Structural Time Series Models and the Kalman Filter
TL;DR: In this article, the Kalman filter and state space models were used for univariate structural time series models to estimate, predict, and smoothen the univariate time series model.
Posted Content
Forecasting, Structural Time Series Models and the Kalman Filter
TL;DR: In this paper, the authors provide a unified and comprehensive theory of structural time series models, including a detailed treatment of the Kalman filter for modeling economic and social time series, and address the special problems which the treatment of such series poses.
Journal ArticleDOI
Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy
Diana Finzi,Monika Hermankova,Theodore C. Pierson,Lucy M. Carruth,Christopher B. Buck,Richard E. Chaisson,Thomas C. Quinn,Karen Chadwick,Joseph B. Margolick,Ron Brookmeyer,Joel E. Gallant,Martin Markowitz,David D. Ho,Douglas D. Richman,Robert F. Siliciano +14 more
TL;DR: In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes, and generally did not show mutations associated with resistance to the relevant antiretroviral drugs.