Inferring genetic interactions from comparative fitness data

Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax, the fungus Aspergillus niger, and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

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Inferring Genetic Interactions From Comparative Fitness Data

10.1101/137372 ◽

2017 ◽

Cited By ~ 1

Author(s):

Kristina Crona ◽

Alex Gavryushkin ◽

Devin Greene ◽

Niko Beerenwinkel

Keyword(s):

Evolutionary Biology ◽

Fitness Landscape ◽

Higher Order ◽

Complete Characterization ◽

Genetic Interactions ◽

Gene Interactions ◽

Rank Orders ◽

Darwinian Fitness ◽

Hiv 1

AbstractDarwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax, the fungus Aspergillus niger, and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

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Lexical landscapes as largein silicodata for examining advanced properties of fitness landscapes

10.1101/640151 ◽

2019 ◽

Author(s):

Victor A. Meszaros ◽

Miles D. Miller-Dickson ◽

C. Brandon Ogbunugafor

Keyword(s):

Evolutionary Theory ◽

Empirical Data ◽

In Silico ◽

Evolutionary Biology ◽

Fitness Landscape ◽

Evolutionary Genetics ◽

Higher Order ◽

Fitness Landscapes ◽

Adaptive Landscape ◽

Data Sets

In silicoapproaches have served a central role in the development of evolutionary theory for generations. This especially applies to the concept of the fitness landscape, one of the most important abstractions in evolutionary genetics, and one which has benefited from the presence of large empirical data sets only in the last decade or so. In this study, we propose a method that allows us to generate enormous data sets that walk the line betweenin silicoand empirical: word usage frequencies as catalogued by the Google ngram corpora. These data can be codified or analogized in terms of a multidimensional empirical fitness landscape towards the examination of advanced concepts—adaptive landscape by environment interactions, clonal competition, higher-order epistasis and countless others. We argue that the greaterLexical Landscapesapproach can serve as a platform that offers an astronomical number of fitness landscapes for exploration (at least) or theoretical formalism (potentially) in evolutionary biology.

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Conditional Probability, Three-Slit Experiments, and the Jordan Algebra Structure of Quantum Mechanics

Advances in Mathematical Physics ◽

10.1155/2012/156573 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 12

Author(s):

Gerd Niestegge

Keyword(s):

Quantum Mechanics ◽

Conditional Probability ◽

Mathematical Structure ◽

Higher Order ◽

Complete Characterization ◽

Jordan Algebras ◽

Algebra Structure ◽

Quantum Logics ◽

Close Link

Most quantum logics do not allow for a reasonable calculus of conditional probability. However, those ones which do so provide a very general and rich mathematical structure, including classical probabilities, quantum mechanics, and Jordan algebras. This structure exhibits some similarities with Alfsen and Shultz's noncommutative spectral theory, but these two mathematical approaches are not identical. Barnum, Emerson, and Ududec adapted the concept of higher-order interference, introduced by Sorkin in 1994, into a general probabilistic framework. Their adaption is used here to reveal a close link between the existence of the Jordan product and the nonexistence of interference of third or higher order in those quantum logics which entail a reasonable calculus of conditional probability. The complete characterization of the Jordan algebraic structure requires the following three further postulates: a Hahn-Jordan decomposition property for the states, a polynomial functional calculus for the observables, and the positivity of the square of an observable. While classical probabilities are characterized by the absence of any kind of interference, the absence of interference of third (and higher) order thus characterizes a probability calculus which comes close to quantum mechanics but still includes the exceptional Jordan algebras.

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Rank orders and signed interactions in evolutionary biology

eLife ◽

10.7554/elife.51004 ◽

2020 ◽

Vol 9 ◽

Author(s):

Kristina Crona

Keyword(s):

Evolutionary Biology ◽

Current Theory ◽

Genetic Interactions ◽

Cancer Drug ◽

Antimalarial Drug Resistance ◽

Species Invasions ◽

Rank Orders ◽

Order Constraints ◽

Cancer Drug Treatment ◽

Ancestral Type

Rank orders have been studied in evolutionary biology for almost a hundred years. Constraints on the order in which mutations accumulate are known from cancer drug treatment, and order constraints for species invasions are important in ecology. However, current theory on rank orders in biology is somewhat fragmented. Here, we show how our previous work on inferring genetic interactions from comparative fitness data (Crona et al., 2017) is related to an influential approach to rank orders based on sign epistasis. Our approach depends on order perturbations that indicate interactions. We apply our results to malaria parasites and find that order perturbations beyond sign epistasis are prevalent in the antimalarial drug-resistance landscape. This finding agrees with the observation that reversed evolution back to the ancestral type is difficult. Another application concerns the adaptation of bacteria to a methanol environment.

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DANGO: Predicting higher-order genetic interactions

10.1101/2020.11.26.400739 ◽

2020 ◽

Author(s):

Ruochi Zhang ◽

Jianzhu Ma ◽

Jian Ma

Keyword(s):

Genetic Interaction ◽

Phenotypic Diversity ◽

Search Space ◽

Higher Order ◽

Genetic Interactions ◽

Combinatorial Search ◽

Pairwise Interactions ◽

Phenotypic Variations ◽

Almost All

AbstractHigher-order genetic interactions, which have profound impact on phenotypic variations, remain poorly characterized. Almost all studies to date have primarily reported pairwise interactions because it is dauntingly difficult to design high-throughput genetic screenings of the large combinatorial search space for higher-order interactions. Here, we develop an algorithm named Dango, based on a self-attention hypergraph neural network, to effectively predict the higher-order genetic interaction for a group of genes. As a proof-of-concept, we make comprehensive prediction of >400 million trigenic interactions in the yeast S. cerevisiae, significantly expanding the quantitative characterization of trigenic interactions. We find that Dango can accurately predict trigenic interactions that reveal both known and new biological functions related to cell growth. The predicted trigenic interactions can also serve as powerful genetic markers to predict growth response to many distinct conditions. Dango enables unveiling a more complete map of complex genetic interactions that impinge upon phenotypic diversity.

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Experimental Characterization of Mechanical Behavior of Cord-Rubber Composites

Tire Science and Technology ◽

10.2346/1.2150974 ◽

1982 ◽

Vol 10 (1) ◽

pp. 37-54 ◽

Cited By ~ 11

Author(s):

M. Kumar ◽

C. W. Bert

Keyword(s):

Response Characteristic ◽

Cord Compression ◽

Complete Characterization ◽

Strain Response ◽

Strain Gages ◽

Experimental Characterization ◽

Rubber Composites ◽

Stress Strain ◽

Strain Data

Abstract Unidirectional cord-rubber specimens in the form of tensile coupons and sandwich beams were used. Using specimens with the cords oriented at 0°, 45°, and 90° to the loading direction and appropriate data reduction, we were able to obtain complete characterization for the in-plane stress-strain response of single-ply, unidirectional cord-rubber composites. All strains were measured by means of liquid mercury strain gages, for which the nonlinear strain response characteristic was obtained by calibration. Stress-strain data were obtained for the cases of both cord tension and cord compression. Materials investigated were aramid-rubber, polyester-rubber, and steel-rubber.

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H∞ performance of weighted interval plants: complete characterization of vertex results

1993 American Control Conference ◽

10.23919/acc.1993.4792931 ◽

1993 ◽

Cited By ~ 3

Author(s):

C. V. Hollot ◽

R. Tempo

Keyword(s):

Complete Characterization ◽

Interval Plants

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Characterization of CMOS Structures (0.6 µm process) Submitted to HBM and COM ESD Stress Tests

ISTFA 1997: Conference Proceedings from the 23rd International Symposium for Testing and Failure Analysis ◽

10.31399/asm.cp.istfa1997p0315 ◽

1997 ◽

Author(s):

G. Meneghesso ◽

E. Zanoni ◽

P. Colombo ◽

M. Brambilla ◽

R. Annunziata ◽

...

Keyword(s):

Electron Microscopy ◽

Electrostatic Discharge ◽

Stress Test ◽

Complete Characterization ◽

Stress Tests ◽

Test Procedures ◽

Emission Microscopy ◽

Fast Rise ◽

Scanning Electron

Abstract In this work, we present new results concerning electrostatic discharge (ESD) robustness of 0.6 μm CMOS structures. Devices have been tested according to both HBM and socketed CDM (sCDM) ESD test procedures. Test structures have been submitted to a complete characterization consisting in: 1) measurement of the tum-on time of the protection structures submitted to pulses with very fast rise times; 2) ESD stress test with the HBM and sCDM models; 3) failure analysis based on emission microscopy (EMMI) and Scanning Electron Microscopy (SEM).

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