Using the Constrained Disorder Principle to Navigate Uncertainties in Biology and Medicine: Refining Fuzzy Algorithms

Biology, Год журнала: 2024, Номер 13(10), С. 830 - 830

Опубликована: Окт. 16, 2024

Uncertainty in biology refers to situations which information is imperfect or unknown. Variability, on the other hand, measured by frequency distribution of observed data. Biological variability adds uncertainty. The Constrained Disorder Principle (CDP) defines all systems universe their inherent variability. According CDP, exhibit a degree necessary for proper function, allowing them adapt changes environments. Per while differs from uncertainty, it can be viewed as regulated mechanism efficient functionality rather than This paper explores various aspects un-certainties biology. It focuses using CDP-based platforms refining fuzzy algorithms address some challenges associated with biological and medical uncertainties. Developing decision tree that considers natural help minimize method reveal previously unidentified classes, reduce number unknowns, improve accuracy modeling results, generate algorithm outputs are more biologically clinically relevant.

Язык: Английский

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Selection and the direction of phenotypic evolution

eLife, Год журнала: 2023, Номер 12

Опубликована: Авг. 31, 2023

Predicting adaptive phenotypic evolution depends on invariable selection gradients and the stability of genetic covariances between component traits multivariate phenotype. We describe six locomotion behavior body size in nematode Caenorhabditis elegans for 50 generations adaptation to a novel environment. show that direction can be predicted from ancestral differentials, particularly when were measured new Interestingly, individual does not always occur selection, nor are trait responses homogeneous among replicate populations. These observations explained because dimension with most standing variation only partially aligns under directional selection. findings validate theory suggest is predictable tens generations.

Язык: Английский

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Metabolic similarity and the predictability of microbial community assembly

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 28, 2023

When microbial communities form, their composition is shaped by selective pressures imposed the environment. Can we predict which will assemble under different environmental conditions? Here, hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable community composition. To end, measured growth rate and by-product profile of a library proteobacterial strains large number single nutrient environments. We found rates secretion profiles were positively correlated when supplied substrate was similar. By analyzing hundreds in-vitro experimentally assembled an array synthetic environments, then show substrates select for taxonomically communities. These findings us propose validate comparative approach quantitatively predicting effects novel on complex consortia.

Язык: Английский

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The Role of Stakeholders’ Understandings in Emerging Antimicrobial Resistance: A One Health Approach

Microorganisms, Год журнала: 2023, Номер 11(11), С. 2797 - 2797

Опубликована: Ноя. 17, 2023

The increasing misuse of antibiotics in human and veterinary medicine agroecosystems the consequent selective pressure resistant strains lead to multidrug resistance (AMR), an expanding global phenomenon. Indeed, this phenomenon represents a major public health target with significant clinical implications related increased morbidity mortality prolonged hospital stays. current presence microorganisms multi-resistant isolated patients is problem because additional burden disease it places on most fragile difficulty finding effective therapies. In recent decades, international organizations like World Health Organization (WHO) European Centre for Disease Prevention Control (ECDC) have played roles addressing issue AMR. ECDC estimates that Union alone, antibiotic causes 33,000 deaths approximately 880,000 cases disability each year. epidemiological impact AMR inevitably also has direct economic consequences not only loss life but reduction number days worked, use healthcare resources diagnostic procedures second-line when available. 2015, WHO, recognising as complex can be addressed by coordinated multi-sectoral interventions, promoted One approach considers human, animal, environmental integrated manner. review, authors try address why collaboration all stakeholders involved growth management necessary order achieve optimal people, animals, plants, environment, highlighting growing threat animal health, food safety security, prosperity, ecosystems worldwide.

Язык: Английский

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Game Theory for Managing Evolving Systems: Challenges and Opportunities of Including Vector-Valued Strategies and Life-History Traits

Dynamic Games and Applications, Год журнала: 2023, Номер 13(4), С. 1130 - 1155

Опубликована: Дек. 1, 2023

Язык: Английский

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Forecasting of phenotypic and genetic outcomes of experimental evolution inPseudomonas syringaeandPseudomonas savastanoi

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 12, 2024

ABSTRACT Microbial experimental evolution is commonly highly repeatable under identical conditions, indicating a potential for short-term evolutionary forecasting. However, it unclear to what extent predictions can be extrapolated related species adapting in similar environments, which would enable direct testing of general forecasting models and biological assumptions. To further develop model system based on adaptation static culture we experimentally tested previous Pseudomonas syringae savastanoi . In addition sequence divergence, these also differ their repertoire diguanylate cyclases that mutationally activated produce the adaptive wrinkly spreader (WS) phenotype genes biosynthesis exopolysaccharides. After evolution, isolated 32 independent WS mutants P. 37 had increased ability colonize air-liquid interface reduced motility. As predicted, most mutations wsp operon followed by rarer promoter upstream uncharacterized cyclases. Surprisingly, no were found wspF, mutated gene previously characterized species, was explained differences relative fitness. While prediction regions largely successful WspA, WspE divergent pattern both species. deletion known exopolysaccharide loci shown contribute other did not reduce fitness, suggesting presence additional adhesive components c-di-GMP control. This study shows forecasts extended but genotype-phenotype-fitness map mutational biases limit predictability detailed molecular level. Author summary Biological often observed short-term, suggests might possible forecast ultimately steer evolution. Evolutionary processes are fundamental biology central major societal problems, including antibiotic resistance, cancer, climate change. Experimental with microbes makes real-time over many generations allow tests forecasts. problem predictive usually data limits novelty beyond simple repeatability. A more challenging issue predict degree evolve ways environments. Here show one best bacterial systems, biofilm formation at surface tubes , evolving allowed us directly test phenotypes evolved details fail. elucidates causes failed continuous improvements delineate

Язык: Английский

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Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs across hundreds of fluconazole-resistant yeast strains

Опубликована: Март 15, 2024

There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common evolution and occur when, for example, resistance one drug results sensitivity another. Major questions remain about the extent which reliable, specifically, whether mutants provide a given all suffer similar tradeoffs. This question difficult because drug-resistant observed clinic, even those evolved controlled laboratory settings, often biased towards large fitness benefits. Thus, mutations (and mechanisms) may be more diverse than current data suggests. Here, we perform experiments utilizing lineage-tracking capture fuller spectrum of give yeast cells advantage fluconazole, antifungal drug. We then quantify each 774 across 12 environments, finding these group into 6 classes with characteristically different Their unique imply affects through underlying mechanisms. Some groupings find surprising. For some resist single drugs do not their combination, same gene have others. These findings, on hand, demonstrate difficulty relying consistent or intuitive when treatments. On other by demonstrating hundreds adaptive can reduced few groups characteristic tradeoffs, our findings empower strategies Finally, grouping likely affect mechanisms, work guides efforts map phenotypic effects mutation.

Язык: Английский

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Mutation bias alters the distribution of fitness effects of mutations

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 27, 2024

ABSTRACT Mutation bias is an important factor determining the diversity of genetic variants available for selection, and can therefore constrain paths to adaptation. An additional constraint emerges over course evolution. As adaptation proceeds some beneficial mutations are fixed, new become rare, limiting further Recent theoretical work predicts that these constraints may be alleviated by a change in direction mutation (i.e., reversal). populations sample previously underexplored types mutations, distribution fitness effects (DFE) should shift towards more mutations. Here, we test this prediction using Escherichia coli , which has transition bias, with ∼55% single-nucleotide being transitions compared unbiased expectation ∼33% transitions. We generated mutant strains wide range biases from 96% 98% transversions, either reinforcing or reversing wild type bias. Quantifying DFEs hundreds single obtained accumulation experiments each strain, find strong support prediction. Strains oppose ancestral transversion bias) have highest proportion whereas exacerbate up 10-fold fewer Such dramatic differences DFE drive large variation rate outcome Our results thus strongly suggest generalized evolutionary role shifts.

Язык: Английский

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Unravelling the factors of evolutionary repeatability: insights and perspectives on predictability in evolutionary biology

Frontiers in Ecology and Evolution, Год журнала: 2024, Номер 12

Опубликована: Апрель 23, 2024

Evolutionary biology was previously considered a historical science with predictions about evolutionary trajectories believed to be near impossible. The development of high throughput sequencing and data analysis technologies has challenged this belief, provided an abundance that yields novel insights into processes. are now increasingly being used develop fundamental knowledge evolving systems and/or demonstrate control. Here we investigate the factors make repeatability more or less likely increase accuracy predictions. We identify outstanding questions provide potential starting point determine how is affected by genetic relatedness.

Язык: Английский

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Divergence time and environmental similarity predict the strength of morphological convergence in stick and leaf insects

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 9, 2023

Abstract Independent evolution of similar traits in lineages inhabiting environments (convergent evolution) is often taken as evidence for adaptation by natural selection, and used to illustrate the predictability evolution. Yet convergence rarely perfect. Environments may not be they appear (e.g., habitats scored same heterogenous organisms). And can evolve different ways even when submitted environmental challenges, because responses selection are contingent upon available genetic variation independent differ alleles, backgrounds, developmental mechanisms responsible phenotypes question. Both impediments predicted increase length time separating two increases, making it difficult discern their relative importance. We quantified similarity extent show how habitat divergence each contribute observed patterns morphological stick leaf insects (order Phasmatodea). Dozens phasmid independently colonized habitats, repeatedly evolving parallel directions on a 26-trait morphospace, though magnitude direction these shifts varied. Lineages converging towards more ended up closer did closely related lineages, followed trajectories arrive there. Remarkably, after accounting similarity, we that reduced at constant rate across than 60 million years separation, suggesting contingency predictable, given sufficient spans time. Significance statement Phasmids (stick insects) exemplify extraordinary power shape organismal phenotypes. The animals themselves charismatic champions crypsis masquerade; our characterization adaptive radiation reveals dozens instances convergence, adapted changes body forms. Our findings conditions experienced organisms – closeness invaded niches elapsed since divergence, both predict strength convergence. an evolutionary process surprisingly have been tens millions years.

Язык: Английский

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