Universality and predictability in molecular quantitative genetics

Nourmohammad, Armita; Held, Torsten; Lässig, Michael

doi:10.1016/j.gde.2013.11.001

Cited by 30 publications

(47 citation statements)

References 80 publications

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“…It is useful to measure phenotypes in natural units, which avoids the arbitrariness of the physical units ({κ i ,κ i }), and the total number of sites +ˆ . As previously shown in [34,64], there exist summary statistics of the site-specific effects, (here {κ i ,κ i }), which define a natural scale of the molecular phenotype. We denote the moments of the site-specific effects along the genome by,…”

Section: Statistics Of the Binding Affinity Distribution For Virus V γmentioning

confidence: 99%

“…Specifically, we model the effects of mutations, selection and reproductive stochasticity on the distribution of binding affinities between the two populations. Projecting from the high-dimensional space of genotypes to lower dimension of binding phenotypes allows for a predictive and analytical description of the coevolutionary process [34], whilst retaining the salient information about the quan-tities of greatest biological and therapeutic interest.…”

Section: Introductionmentioning

confidence: 99%

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Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections

2016

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The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics between antibodies and antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may have relevance to vaccine design against HIV.

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Section: Statistics Of the Binding Affinity Distribution For Virus V γmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections

2016

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“…, M ) with a time separation τ ≡ t i+1 − t i . We define a stationary cost-to-go function, J(x, tm; τ ) = min (13) where the devision by the total time M τ assures that the cost-to-go remains finite. To further simplify, we only consider one dimensional phenotype x with intrapopulation variance k, the cost of deviation V (x) = g(x − x * ) 2 /2 from target x * , and the cost of intervention βu 2 /2 with artificial selection u.…”

Section: F Artificial Selection With Intermittent Monitoringmentioning

confidence: 99%

Optimal evolutionary control for artificial selection on molecular phenotypes

Nourmohammad

Eksin

2019

Preprint

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Controlling an evolving population is an important task in modern molecular genetics, including in directed evolution to improve the activity of molecules and enzymes, breeding experiments in animals and in plants, and in devising public health strategies to suppress evolving pathogens. An optimal intervention to direct evolution should be designed by considering its impact over an entire stochastic evolutionary trajectory that follows. As a result, a seemingly suboptimal intervention at a given time can be globally optimal as it can open opportunities for desirable actions in the future. Here, we propose a feedback control formalism to devise globally optimal artificial selection protocol to direct the evolution of molecular phenotypes. We show that artificial selection should be designed to counter evolutionary tradeoffs among multi-variate phenotypes to avoid undesirable outcomes in one phenotype by imposing selection on another. Control by artificial selection is challenged by our ability to predict molecular evolution. We develop an information theoretical framework and show that molecular time-scales for evolution under natural selection can inform how to monitor a population to acquire sufficient predictive information for an effective intervention with artificial selection. Our formalism opens a new avenue for devising optimal artificial selection for directed evolution of molecular functions.

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“…A similar approach is feasible for the force-moment and the combined ensembles. Generalised canonical ensembles of this kind are used in statistical genetics [23,24]. The qualitative impact of these modifications on the resulting thermodynamics is small.…”

Section: B Generalised (Protocol Dependent) Ensemblesmentioning

confidence: 99%

Protocol-independent granular temperature supported by numerical simulations

Kassner

2015

Phys. Rev. E

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A possible approach to the statistical description of granular assemblies starts from Edwards's assumption that all blocked states occupying the same volume are equally probable [Edwards and Oakeshott, Physica A 157, 1080 (1989)]. We performed computer simulations using two-dimensional polygonal particles excited periodically according to two different protocols: excitation by pulses of "negative gravity" and excitation by "rotating gravity." The first protocol exhibits a nonmonotonous dependency of the mean volume fraction on the pulse strength. The overlapping histogram method is used in order to test whether the volume distribution is described by a Boltzmann-like distribution and to calculate the inverse compactivity as well as the logarithm of the partition sum. We find that the mean volume is a unique function of the measured granular temperature, independently of the protocol and of the branch in ϕ(g), and that all determined quantities are in agreement with Edwards's theory.

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Universality and predictability in molecular quantitative genetics

Cited by 30 publications

References 80 publications

Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections

Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections

Optimal evolutionary control for artificial selection on molecular phenotypes

Protocol-independent granular temperature supported by numerical simulations

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