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Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype↗

Initial state randomness improves sequence learning in a model hippocampal network.

Randomness can be a useful component of computation. Using a computationally minimal, but still biologically based model of the hippocampus, we evaluate the effects of initial state randomization on learning a cognitive problem that requires this brain structure. Greater randomness of initial states leads to more robust performance in simulations of the cognitive task called transverse patterning, a context-dependent discrimination task that we code as a sequence prediction problem. At the conclusion of training, greater initial randomness during training trials also correlates with increased, repetitive firing of select individual neurons, previously named local context neurons. In essence, such repetitively firing neurons recognize subsequences, and previously their presence has been correlated with solving the transverse patterning problem. A more detailed analysis of the simulations across training trials reveals more about initial state randomization. The beneficial effects of initial state randomization derive from enhanced variation, across training trials, of the sequential states of a network. This greater variation is not uniformly present during training; it is largely restricted to the beginning of training and when novel sequences are introduced. Little such variation occurs after extensive or even moderate amounts of training. We explain why variation is high early in training, but not later. This automatic modulation of the initial-state-driven random variation through state space is reminiscent of simulated annealing where modulated randomization encourages a selectively broad search through state space. In contrast to an annealing schedule, the selective occurrence of such a random search here is an emergent property, and the critical randomization occurs during training rather than testing.

Animals↗

Dissociation of processes underlying spatial s-r compatibility: evidence for the independent influence of what and where.

The process-dissociation procedure was used to estimate the influence of spatial and form-based processing in the Simon task. Subjects made manual (left/right) responses to the direction of arrows (> or <) presented to the left or right of fixation. Manipulating the proportion of incongruent trials (e.g., a right-pointing arrow presented to the left of fixation) affected both the size and direction of the Simon effect. To account for this pattern of data, we compared process estimates based on three possible relationships between spatial and form-based processing: independence, redundancy, and exclusivity. The independence model provided the best account of the data. Most telling was that independent form-based estimates were superior at predicting observed performance on arrows presented at fixation and did so consistently across conditions (r's > .80). The results provide evidence that the form ("what") and spatial location ("where") of a single stimulus can have functionally independent effects on performance. They also indicate the existence of two kinds of automaticity--an associative ("implicit learning") component that reflects prior S-R mappings and a nonassociative component that reflects the correspondence between stimulus and response codes.

Cognition↗

Configural processing in memory retrieval: multiple cues and ensemble representations.

When retrieving information from memory, a number of contextual cues may interact to determine which ideas will be easily accessible. Even the simplest case in which joint cue action obtains (two cues) is very revealing of the principles of memory access and representation of compounds. Mechanisms by which dual cues interact to constrain retrieval from episodic memory are considered. A holistic mechanism of cue integration is contrasted with two nonholistic mechanisms: a multiplicative or intersection mechanism and an independent-contributions mechanism. Holistic- and intersection-cuing mechanisms are consistent with different variants of compound cue models of priming. The independent cuing mechanism is consistent with spreading activation models of priming. Data from four experiments which examined dual-cued recognition of items from (newly learned) triples demonstrated strongly configural, holistic, action of dual cues. The two cues and test item must form an encoded compound to yield cuing advantages. Two independent cues to the test item are ineffective if the two cues and test were not learned together as a triple; one valid and one invalid cue are also ineffective. This is so despite the availability of pairwise information for each cue-test relation, and despite the fact that these cues are effective when operating alone. A compound cue model which predicts precisely this surprising pattern of priming is developed. The compound cue model also predicts previously obtained configural priming of associative judgments, as well as the bias priming generally observed in item recognition and similar paradigms.

Analysis of Variance↗

Predictors of adoption and maintenance of vigorous physical activity in men and women.

BACKGROUND: This study examined predictors of adoption and maintenance of vigorous physical activity over time in a sample of 1,719 randomly selected women and men. METHODS: Based on reported frequency of vigorous exercise in a mail survey at baseline, subjects were classified as sedentary (zero sessions per week), intermediate (one to two sessions per week), or active (three or more sessions per week). RESULTS: On the same survey subjects reported on 25 potential determinants of physical activity based on a comprehensive learning model. Twenty-four months later, 85% of subjects were resurveyed, and their physical activity levels were classified. Within each baseline category and gender subgroup, predictors of follow-up physical activity were identified. In multivariate analyses, adoption of vigorous exercise by sedentary men was predicted by self-efficacy, age (inverse), and neighborhood environment (inverse). Adoption by sedentary women was predicted by education, self-efficacy, and friend and family support for exercise. Maintenance of vigorous physical activity was predicted by self-efficacy and age (inverse) for initially active men and by education for initially active women. CONCLUSION: These results suggest that factors influencing adoption are different for men and women, and there may be different factors influencing adoption versus maintenance of vigorous physical activity.

Adult↗

Adaptation of visually guided behavior during reversed vision in schizophrenia: a preliminary study.

This preliminary study evaluated the adaptation of visually guided behavior to reversed vision in schizophrenia. The study included 54 patients who met DSM-III-R criteria for schizophrenia. Visuomotor reaction times (VRTs) during reversed vision were measured in six blocks of 35 consecutive trials. The VRTs of schizophrenics were compared with those of normal subjects. A good fit (R2 = 0.9981) for the adaptation process of VRTs during reversed vision was found with the equation y = 1030 + 1499/x, where x is the order of the block and y is the group mean VRT for each block. The VRTs in schizophrenics were significantly slower than those in normal subjects. However, the adaptation process to reversed vision essentially did not differ from normal. The adaptation of visually guided behavior during reversed vision may involve procedural learning; this task may thus be useful in evaluating such learning. The VRTs during reversed vision may be related to some aspects of symptoms in the patient with schizophrenia and may also be useful in predicting clinical outcome.

Adult↗

Fine motor dexterity is correlated to social functioning in schizophrenia.

OBJECTIVE: To identify neuropsychological domains, including fine motor dexterity, that are related to social functioning in schizophrenia. METHOD: Thirty-six DSM-IV schizophrenic subjects were assessed using the Purdue Pegboard test, the Modified Wisconsin Card Sorting test, the Tower of London, Schwartz' Reaction Time and Wechsler's Associate Learning and Digit Span tests. Social functioning was measured by the Social and Occupational Functional Assessment Scale. RESULTS: Univariate regression analyses showed that the Purdue Pegboard, the Modified Card Sorting test, the Tower of London and Wechsler's Associate Learning subtest were significantly linked to social functioning. The best fitting multivariate model to explain social functioning included fine motor dexterity and executive functioning. CONCLUSION: Various neuropsychological measures correlated to social functioning, the correlation involving fine motor dexterity being the strongest one. Future studies of the prediction of social functioning in schizophrenia should include fine motor dexterity.

Cognition Disorders↗

Is numerical comparison digital? Analogical and symbolic effects in two-digit number comparison.

Do Ss compare multidigit numbers digit by digit (symbolic model) or do they compute the whole magnitude of the numbers before comparing them (holistic model)? In 4 experiments of timed 2-digit number comparisons with a fixed standard, the findings of Hinrichs, Yurko, and Hu (1981) were extended with French Ss. Reaction times (RTs) decreased with target-standard distance, with discontinuities at the boundaries of the standard's decade appearing only with standards 55 and 66 but not with 65. The data are compatible with the holistic model. A symbolic interference model that posits the simultaneous comparison of decades and units can also account for the results. To separate the 2 models, the decades and units digits of target numbers were presented asynchronously in Experiment 4. Contrary to the prediction of the interference model, presenting the units before the decades did not change the influence of units on RTs. Pros and cons of the holistic model are discussed.

Adult↗

The relationship between short-term memory and working memory: complex span made simple?

This experiment addresses the question of what makes a working memory measure a good predictor of higher-level abilities. Verbal and visuospatial processing episodes were interleaved with distinct verbal and visuospatial storage episodes to form four complex span tasks. Although these measures were reliable predictors of reading and mathematics ability in children, they were no more predictive of these abilities than corresponding simple span tasks involving storage alone. However, when individual differences in storage ability and processing capacity were controlled for, residual variance in complex span performance was related to academic ability in some cases. These findings indicate that complex span tasks are multiply determined, and that differences in task structure can dramatically influence the relative importance of these multiple constraints and the predictive power of a complex span measure.

Child↗

What we have learned about prokaryotes from structural genomics.

Five years ago systematic determination and theoretical analysis of all protein structures encoded in model prokaryotic organisms was proposed as a powerful way to obtain new insights into protein function and the variety of protein folds. What has been the pay-off from studying structures in genomic context? Have we learned anything new about protein structure? Can we now predict protein function better? In this contribution, I summarize the status of large-scale structure determination projects on prokaryotes and provide an overview of the main results obtained from experimental and theoretical studies in this dynamic research field.

Bacterial Proteins↗

Machine learning techniques for in silico modeling of drug metabolism.

The computational assessment of drug metabolism has gained considerable interest in pharmaceutical research. Amongst others, machine learning techniques have been employed to model relationships between the chemical structure of a compound and its metabolic fate. Examples for these techniques, which were originally developed in fields far from drug discovery, are artificial neural networks or support vector machines. This paper summarizes the application of various machine learning techniques to predict the interaction between organic molecules and metabolic enzymes. More complex endpoints such as metabolic stability or in vivo clearance will also be addressed. It is shown that the prediction of metabolic endpoints with machine learning techniques has made considerable progress over the past few years. Depending on the procedure used, either classification or quantitative prediction is possible for even large and diverse compound sets. Together with the expanding experimental data basis, these in silico methods have become valuable tools in the drug discovery and development process.

Artificial Intelligence↗

Learning styles of students and faculty in selected health care professions.

The purposes of this study were to determine if students and faculty in nursing and allied health demonstrate a predominant learning style, if there is an association between a specific learning style (converger, diverger, accommodator, or assimilator) and self-directed learning readiness for these groups, if these learning characteristics can predict academic success, and if a discipline-specific learning style can be identified. Marshall and Merritt's (1986) Learning Style Questionnaire and Guglielmino's (1978) Self-Directed Learning Readiness Scale (SDLRS) were administered to 301 generic BSN students, 188 RN-BSN students, 110 allied health students, and 30 nursing faculty from one southwestern university. There were no significant differences in learning style between students and faculty; the converger style was the predominant learning style for all subjects. Faculty were more self-directed than students; although, overall, students scored high on the SDLRS. Self-directed learning readiness appears to affect learning style. Convergers were significantly more self-directed than either the accommodators, assimilators, or divergers. Academic success, as determined by program completion, could not be predicted on the basis of learning style or self-direction.

Adult↗

Animal models of depression: an overview.

Although animal models cannot replicate human psychopathology in every detail, they should properly be conceived as experimental systems in which selected and specific questions can be investigated in ways impossible to do in humans. In considering the general kinds of animal models, distinctions must be drawn among those designed to simulate specific signs or symptoms, those designed to test a specific etiological theory, those designed to study underlying behavioral and neurobiological mechanisms, and those whose principal purpose is to permit pre-clinical drug evaluation. If, for example, drug evaluation is the first concern, the empirical validity of the model in predicting the therapeutic efficacy of drugs is primary, whereas the mechanisms responsible for inducing the syndrome, and behavioral similarity issues become secondary. The available models of depression are reviewed in the light of their specific advantages and limitations, including those induced pharmacologically, maternal and peer separation, learned helplessness, chronic stress, changes in dominance hierarchy, intra-cranial self-stimulation, conditioned motionlessness and behavioral despair models. Since multiple variables are involved in the etiology of depressions, animal models offer the possibility of evaluating their main effects and interactions in a controlled prospective manner. While caution is required in cross-species reasoning, there are nevertheless guidelines, and the continuing development of a comparative approach in Psychiatry has great potential.

Animals↗

Decoding synapses.

The strength of many synapses is modified by various use and time-dependent processes, including facilitation and depression. A general description of synaptic transfer characteristics must account for the history-dependence of synaptic efficacy and should be able to predict the postsynaptic response to any temporal pattern of presynaptic activity. To generate such a description, we use an approach similar to the decoding method used to reconstruct a sensory input from a neuronal firing pattern. Specifically, a mathematical fit of the postsynaptic response to an isolated action potential is multiplied by an amplitude factor that depends on a time-dependent function summed over all previous presynaptic spikes. The amplitude factor is, in general, a nonlinear function of this sum. Approximate forms of the time-dependent function and the nonlinearity are extracted from the data, and then both functions are constructed more precisely by a learning algorithm. This approach, which should be applicable to a wide variety of synapses, is applied here to several crustacean neuromuscular junctions. After training on data from random spike sequences, the method predicts the postsynaptic response to an arbitrary train of presynaptic action potentials. Using a model synapse, we relate the functions used in the fit to underlying biophysical processes. Fitting different neuromuscular junctions allows us to compare their responses to sequences of action potentials and to contrast the time course and degree of facilitation or depression that they exhibit.

Action Potentials↗

Integration of Infant Metabolite, Genetic, and Islet Autoimmunity Signatures to Predict Type 1 Diabetes by Age 6 Years.

CONTEXT: Biomarkers that can accurately predict risk of type 1 diabetes (T1D) in genetically predisposed children can facilitate interventions to delay or prevent the disease. OBJECTIVE: This work aimed to determine if a combination of genetic, immunologic, and metabolic features, measured at infancy, can be used to predict the likelihood that a child will develop T1D by age 6 years. METHODS: Newborns with human leukocyte antigen (HLA) typing were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY). TEDDY ascertained children in Finland, Germany, Sweden, and the United States. TEDDY children were either from the general population or from families with T1D with an HLA genotype associated with T1D specific to TEDDY eligibility criteria. From the TEDDY cohort there were 702 children will all data sources measured at ages 3, 6, and 9 months, 11.4% of whom progressed to T1D by age 6 years. The main outcome measure was a diagnosis of T1D as diagnosed by American Diabetes Association criteria. RESULTS: Machine learning-based feature selection yielded classifiers based on disparate demographic, immunologic, genetic, and metabolite features. The accuracy of the model using all available data evaluated by the area under a receiver operating characteristic curve is 0.84. Reducing to only 3- and 9-month measurements did not reduce the area under the curve significantly. Metabolomics had the largest value when evaluating the accuracy at a low false-positive rate. CONCLUSION: The metabolite features identified as important for progression to T1D by age 6 years point to altered sugar metabolism in infancy. Integrating this information with classic risk factors improves prediction of the progression to T1D in early childhood.

Autoantibodies↗

A learning model of addiction.

Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classically conditioned responses produced by drugs are complex and bi-directional. There has been progress in classifying and predicting the types of conditioned responses, but little is known of mechanisms. New techniques for understanding brain function such as micro-dialysis probes in animals and advanced imaging techniques (PET and SPECT) in human subjects may be utilized in conditioning paradigms to "open the black box." Because the existence of conditioned responses in drug users is now well-established, clinical studies have been instituted to determine whether modification of conditioned responses can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8 week outpatient treatment program.

Affect↗

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries↗

Stressor-provoked behavioral changes in six strains of mice.

Behavioral changes induced by inescapable shock were examined in six strains of mice. Exposure to shock provoked time-dependent disturbances of shuttle escape performance. In some strains the shock treatment did not affect escape performance, whereas in others profound performance deficits were evident. The inescapable shock treatment likewise induced strain-dependent alterations of performance in a forced-swim task. In most instances the shock treatment initially provoked invigorated responding, but in other strains the shock had no effect or depressed active responding. Finally, Y-maze spontaneous alteration performance was not affected by the shock treatment, although a strain-dependent increase of perseverative responses was evident. The occurrence of a stressor-induced deficit in one task in a particular strain of mouse was not predictive of behavioral alterations in a second task. These data are discussed with respect to animal models of depression and genetic differences associated with the response to stressors.

Animals↗