Tunable kinetic proofreading in a model with molecular frustration

Lindo, André M.; Faria, Bruno; Abreu, F. Vistulo de

doi:10.1007/s12064-011-0134-z

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…This happened because generalized kinetic proofreading mechanisms were identified [42, 43, 60] making each T cell a context discriminator (or detector). Indeed, in [60] it was shown that in CFSs the dissociation constant that distinguishes alternative pathways before major signals are produced [61] is renormalized by factors related to cell frequencies in the population. The production of major signals was straightforwardly related to long-lived conjugations and it was proposed that the focus for understanding how the adaptive immune system works should be placed on which cells establish those long-lived conjugations.…”

Section: Discussionmentioning

confidence: 99%

Can the Immune System Perform a t-Test?

2017

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The self-nonself discrimination hypothesis remains a landmark concept in immunology. It proposes that tolerance breaks down in the presence of nonself antigens. In strike contrast, in statistics, occurrence of nonself elements in a sample (i.e., outliers) is not obligatory to violate the null hypothesis. Very often, what is crucial is the combination of (self) elements in a sample. The two views on how to detect a change seem challengingly different and it could seem difficult to conceive how immunological cellular interactions could trigger responses with a precision comparable to some statistical tests. Here it is shown that frustrated cellular interactions reconcile the two views within a plausible immunological setting. It is proposed that the adaptive immune system can be promptly activated either when nonself ligands are detected or self-ligands occur in abnormal combinations. In particular we show that cellular populations behaving in this way could perform location statistical tests, with performances comparable to t or KS tests, or even more general data mining tests such as support vector machines or random forests. In more general terms, this work claims that plausible immunological models should provide accurate detection mechanisms for host protection and, furthermore, that investigation on mechanisms leading to improved detection in “in silico” models can help unveil how the real immune system works.

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Section: Discussionmentioning

confidence: 99%

Can the Immune System Perform a t-Test?

2017

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“…One of these, based on "energy relay" will be discussed later in this section. Another kinetic proofreading scheme [259] is based on "inter-molecular frustration".…”

Section: Specificity Amplification By Energy Dissipation: Kinetic Pro...mentioning

confidence: 99%

Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

Chowdhury

2012

Preprint

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A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors "transduce" input energy into mechanical work. All the nanomotors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multimodule motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade "macromolecules of life". We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motordriven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.

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“…Important consequences can result if major events in a population only take place when agents are matched for a minimum amount of time. This happens for certain reactions in biomolecular systems [38, 39], the cellular activation in immunology [1, 40, 41] or reproduction in evolutionary biology populations [42]). Then, it becomes clear that, despite the fact that all agents continuously interact, some will never react.…”

Section: Brief Introduction To the Cellular Frustration Frameworkmentioning

confidence: 99%

Cellular frustration algorithms for anomaly detection applications

Faria

Abreu

2019

PLoS ONE

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Cellular frustrated models have been developed to describe how the adaptive immune system works. They are composed by independent agents that continuously pair and unpair depending on the information that one sub-set of these agents display. The emergent dynamics is sensitive to changes in the displayed information and can be used to detect anomalies, which can be important to accomplish the immune system main function of protecting the host. Therefore, it has been hypothesized that these models could be adequate to model the immune system activation. Likewise it has been hypothesized that these models could provide inspiration to develop new artificial intelligence algorithms for data mining applications. However, computational algorithms do not need to follow strictly the immunological reality. Here, we investigate efficient implementation strategies of these immune inspired ideas for anomaly detection applications and use real data to compare the performance of cellular frustration algorithms with standard implementations of one-class support vector machines and deep autoencoders. Our results demonstrate that more efficient implementations of cellular frustration algorithms are possible and also that cellular frustration algorithms can be advantageous for semi-supervised anomaly detection applications given their robustness and accuracy.

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Tunable kinetic proofreading in a model with molecular frustration

Cited by 4 publications

References 18 publications

Can the Immune System Perform a t-Test?

Can the Immune System Perform a t-Test?

Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

Cellular frustration algorithms for anomaly detection applications

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