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GiantHost: a domain-adaptive and uncertainty-aware framework for giant virus host prediction.

MOTIVATION: Nucleocytoplasmic large DNA viruses (NCLDVs) play crucial roles in global ecosystems. Although metagenomics has vastly accelerated the discovery of novel NCLDVs, predicting their hosts from fragmented contigs remains a critical bottleneck, with no dedicated end-to-end computational tools currently available. Addressing this gap requires overcoming three fundamental challenges: the extreme scarcity of labeled reference genomes, the severe domain shift between laboratory isolates and diverse environmental metagenomes, and the inability of traditional deterministic models to quantify prediction uncertainty-a crucial requirement for reliable ecological profiling where novel, divergent viruses are prevalent. RESULTS: We present GiantHost, the first NCLDV host prediction tool with domain adaptation and uncertainlty awareness. GiantHost employs a dual-tower neural network to integrate dense genome traits and sparse GVOG profiles, allowing better integration of heterogeneous features. To overcome label scarcity and domain shift, we leverage 1400 environmental viral genomes (GVMAGs) via semi-supervised multi-task learning and Domain Adversarial Neural Networks (DANN), effectively bridging the distributional gap between RefSeq and environmental data. Additionally, GiantHost incorporates Conformal Prediction (CP) to output statistically guaranteed prediction sets rather than overconfident single labels. Evaluated under rigorous genome-level cross-validation, GiantHost demonstrates robust predictive power. Applied to the Tara Ocean dataset, GiantHost successfully captured the vertical stratification of NCLDV hosts-revealing a depth-dependent decline of phytoplankton-infecting viruses and a relative enrichment of Amoebozoa-infecting viruses in the mesopelagic zone. AVAILABILITY: The source code of GiantHost is available via: https://github.com/FuchuanQu/GiantHost.

Giant Viruses

Crossmatch prediction of highly sensitized patients.

1. A subset of negative reactions of sera from highly sensitized patients to donor lymphocytes are predicted with high accuracy (96.5% negative correct). 2. The prediction is performed by a hybrid expert system (HES) which uses multiple knowledge of stochastic (SCORES), artificial neural net (ANN), and genetic algorithm (GA) techniques. 3. All knowledge for the T-cell predictions is derived from serological reactions of the investigated sera (93) to a large panel (284). 4. When analyzing 5 HLA Class I typing sera controls, HES performs better than a standard serum analysis method in 3 measurement categories: r value; percent correct; and percent negative correct. 5. SCORES and ANN produce the strongest complementary association. SCORES is the best method with low PRA sera, while ANN is better at predicting high PRA sera. GA performs very poorly with high PRA sera. 6. HES can acquire knowledge from any of the various methods used for serum screening and crossmatch testing. Therefore, there is no need for method standardization as each laboratory will produce its own program incorporating its patients' data. High standardization of HLA Class I typing is necessary. 7. Most recipients for whom donors are never selected by HES are in the PRA range of 97-100%. 8. Certainty level categorization of a crossmatch gives clinical flexibility in judgement of potential donors. 9. All programs are written in the C language and are portable to numerous platforms. HES is implemented on an inexpensive IBM-PC compatible computer and can calculate predictions quickly. 10. HES predicts negative crossmatches with enough accuracy to initiate an organ sharing protocol to increase the chance for highly sensitized patients to obtain a transplant.

Algorithms

Synthetic neural modeling applied to a real-world artifact.

We describe the general design, operating principles, and performance of a neurally organized, multiply adaptive device (NOMAD) under control of a nervous system simulated in a computer. The complete system, Darwin IV, is the latest in a series of models based on the theory of neuronal group selection, which postulates that adaptive behavior is the result of selection in somatic time among synaptic populations. The simulated brain of Darwin IV includes visual and motor areas that are connected with NOMAD by telemetry. Under suitable conditions, Darwin IV can be trained to track a light moving in a random path. After such training, it can approach colored blocks and collect them to a home position. Following a series of contacts with such blocks, value signals received through a "snout" that senses conductivity allow it to sort these blocks on the basis of differences in color associated with differences in their conductivity. Darwin IV represents a new approach to synthetic neural modeling (SNM), a technique in which large-scale computer simulations are employed to analyze the interactions among the nervous system, the phenotype, and the environment of a designed organism as behavior develops. Darwin IV retains the advantages of SNM while avoiding the difficulties and pitfalls of attempting to simulate a rich environment in addition to a brain.

Behavior

Lexical access and the brain: anatomical constraints on cognitive models of word recognition.

Recent studies in the cognitive psychology of reading and many other skilled performances have been dominated by models inspired by neural connectivity (e.g., McClelland & Rumelhart, 1986). Such models have not yet begun to consider the accumulating evidence of considerable anatomical localization of component cognitive operations in the human brain (e.g., Posner, Petersen, Fox, & Raichle, 1988). In this article we apply anatomical findings to the job of building computational models of visual word recognition. Brain imaging studies already provide important constraints on how lexical access should be defined in terms of isolable encoding operations that compute the visual form, phonology, and semantics of words. Brain imaging studies also speak to issues of modularity versus interaction between these encoding operations, distribution versus localization of processing within the operations, and orchestration of operations to accomplish different word processing tasks. We conclude that a combined cognitive and anatomical analysis may be of considerable benefit in developing more adequate models of human information processing.

Brain

EEG classification by learning vector quantization.

EEG classification using Learning Vector Quantization (LVQ) is introduced on the basis of a Brain-Computer Interface (BCI) built in Graz, where a subject controlled a cursor in one dimension on a monitor using potentials recorded from the intact scalp. The method of classification with LVQ is described in detail along with first results on a subject who participated in four on-line cursor control sessions. Using this data, extensive off-line experiments were performed to show the influence of the various parameters of the classifier and the extracted features of the EEG on the classification results.

Algorithms

An investigation of tumor 1H nuclear magnetic resonance spectra by the application of chemometric techniques.

1H nuclear magnetic resonance (NMR) spectra of tumors and normal tissue include signals from all hydrogen-containing metabolites and can therefore be considered multicomponent multivariate mixtures. We have obtained 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney, and spleen) and five rat tumors (GH3 prolactinoma, Morris hepatomas 7777 and 9618a, LBDS1 fibrosarcoma, and Walker 256 carcinosarcoma). We have applied several different chemometric methods to analyze the data. First, we used principal component analysis, cluster analysis, and an optimized artificial neural network to develop a classification rule from a training set of samples of known origin or class. The classification rule was then assessed using a set of unknown samples. We were able to successfully determine the class of each unknown sample. Second, we used the chemometric techniques of factor analysis followed by target testing to investigate the underlying biochemical differences that are detected between the classes of samples.

Adenocarcinoma

Simulating vestibular compensation using recurrent back-propagation.

Vestibular compensation is simulated as learning in a dynamic neural network model of the horizontal vestibulo-ocular reflex (VOR). The bilateral, three-layered VOR model consists of nonlinear units representing horizontal canal afferents, vestibular nuclei (VN) neurons and eye muscle motoneurons. Dynamic processing takes place via commissural connections that link the VN bilaterally. The intact network is trained, using recurrent back-propagation, to produce the VOR with velocity storage integration. Compensation is simulated by removing vestibular afferent input from one side and retraining the network. The time course of simulated compensation matches that observed experimentally. The behavior of model VN neurons in the compensated network also matches real data, but only if connections at the motoneurons, as well as at the VN, are allowed to be plastic. The dynamic properties of real VN neurons in compensated and normal animals are found to differ when tested with sinusoidal but not with step stimuli. The model reproduces these conflicting data, and suggests that the disagreement may be due to VN neuron nonlinearity.

Algorithms

Evidence of hyperplanes in the genetic learning of neural networks.

Genetic Algorithms have been successfully applied to the learning process of neural networks simulating artificial life. In previous research we compared mutation and crossover as genetic operators on neural networks directly encoded as real vectors (Manczer and Parisi 1990). With reference to crossover we were actually testing the building blocks hypothesis, as the effectiveness of recombination relies on the validity of such hypothesis. Even with the real genotype used, it was found that the average fitness of the population of neural networks is optimized much more quickly by crossover than it is by mutation. This indicated that the intrinsic parallelism of crossover is not reduced by the high cardinality, as seems reasonable and has indeed been suggested in GA theory (Antonisse 1989). In this paper we first summarize such findings and then propose an interpretation in terms of the spatial correlation of the fitness function with respect to the metric defined by the average steps of the genetic operators. Some numerical evidence of such interpretation is given, showing that the fitness surface appears smoother to crossover than it does to mutation. This confirms indirectly that crossover moves along privileged directions, and at the same time provides a geometric rationale for hyperplanes.

Algorithms

Information maintenance and statistical dependence reduction in simple neural networks.

This study compares the ability of excitatory, feed-forward neural networks to construct good transformations on their inputs. The quality of such a transformation is judged by the minimization of two information measures: the information loss of the transformation and the statistical dependency of the output. The networks that are compared differ from each other in the parametric properties of their neurons and in their connectivity. The particular network parameters studied are output firing threshold, synaptic connectivity, and associative modification of connection weights. The network parameters that most directly affect firing levels are threshold and connectivity. Networks incorporating neurons with dynamic threshold adjustment produce better transformations. When firing threshold is optimized, sparser synaptic connectivity produces a better transformation than denser connectivity. Associative modification of synaptic weights confers only a slight advantage in the construction of optimal transformations. Additionally, our research shows that some environments are better suited than others for recording. Specifically, input environments high in statistical dependence, i.e. those environments most in need of recoding, are more likely to undergo successful transformations.

Action Potentials

A unified neural network [corrected] model of spatiotemporal processing in X and Y retinal ganglion cells. I. Analytical results.

This work presents unified analyses of spatial and temporal visual information processing in a feed-forward network of neurons that obey membrane, or shunting equations. The feed-forward shunting network possesses properties that make it well suited for processing of static, spatial information. However, it is shown here that those same properties of the shunting network that lead to good spatial processing imply poor temporal processing characteristics. This article presents an extension of the feed-forward shunting network model that solves this problem by means of preprocessing layers. The anatomical interpretation of the resulting model is structurally analogous to recently discovered data on a retinal circuit connecting cones to retinal ganglion cells through pairs of push-pull bipolar cells. Mathematical analysis of the lumped model leads to the hypothesis that X and Y retinal ganglion cells may consist of a single mechanism acting in different parameter ranges. This hypothesis is confirmed in the companion article, wherein the model--in conjunction with a nonlinear temporal adaptation mechanism--is used to reproduce experimental data of both X and Y cells by simple changes in morphological and physiological parameters.

Mathematics

A unified neural network model of spatiotemporal processing in X and Y retinal ganglion cells. II. Temporal adaptation and simulation of experimental data.

This article makes use of a push-pull shunting network, which was introduced in the companion article, to model certain properties of X and Y retinal ganglion cells. Input to the push-pull network is preprocessed by a nonlinear mechanism for temporal adaptation, which is ascribed here to photoreceptor dynamics. The complete circuit is used to show that a simple change in receptive field morphology within a single model equation can change the network's response characteristics to closely resemble those of either X or Y cells. Specifically, an increase in width of the receptive field center mechanism is sufficient to account for generation of on-off (Y-like) instead of null (X-like) responses to modulated gratings. In agreement with experimental data, the Y cell on-off response is independent of spatial phase. Also, the model accurately predicts that on-off responses can be observed in X cells for particular stimulus configurations. Taken together, the results show how the retina combines individually inadequate modules to efficiently handle the tasks required for accurate spatial and temporal visual information processing. The model is also able to clarify a number of controversial experimental findings on the nature of spatiotemporal visual processing in the retina.

Adaptation, Physiological

"Live" neuron and optimal learning rule.

A concept of the live unit as an automatic regulation system with a few admissible states areas in the space of states is considered. Energetic profit of oscillatory behavior consisting in the consecutive transitions of system from one admissible states area to another is shown. It is stated, that external disturbances cause the energy consumption of oscillatory system to decrease. On the basis of this concept and some neurophysiological data, the "live" energy-consuming nonlinear three-state neuron model is proposed and the existence of energy optimal generation frequency v(opt) is proved. For the realization of tendency to v(opt) the optimal learning rule is proposed, which provides unsupervised learning and interlinked short-term and long-term memories with forgetting. The model proposed explains the genesis of neural network, is promising in the sense of network self-organization and allows to solve the problem of internal activity in the researches on artificial intelligence.

Biological Clocks

Self-organization of day cycle and hierarchical associative memory in "live" neural network.

The "live" neural network model is proposed on the basis of "live" neuron model and optimal learning rule. By means of numerical simulation the initial stages of neural network self-organization have been shown: (1) the formation of two activity forms, which are identified with sleep and awaking, and (2) the self-organization of hierarchical associative memory when feeding a receptor excitation to the neural network. The energetic profit of self-organization is demonstrated. The formation of neural ensembles, playing the role of generalized neurons, is obtained.

Biological Clocks

On the performance of single-layered neural networks.

This paper studies the performance of single-layered neural networks. This study begins with the performance of single-layered neural networks trained using the outer-product rule. The outer-product rule is a suboptimal learning scheme, resulting under certain assumptions from optimal least-squares training of single-layered neural networks with respect to their analog output. Extensive analysis reveals the improvement on the network performance caused by its optimal least-squares training. The effect of the training scheme on the performance of single-layered neural networks with binary output is exhibited by experimentally comparing the performance of single-layered neural networks trained with respect to their analog and binary output.

Mathematics

Bifurcation analysis of a neural network model.

This paper describes the analysis of the well known neural network model by Wilson and Cowan. The neural network is modeled by a system of two ordinary differential equations that describe the evolution of average activities of excitatory and inhibitory populations of neurons. We analyze the dependence of the model's behavior on two parameters. The parameter plane is partitioned into regions of equivalent behavior bounded by bifurcation curves, and the representative phase diagram is constructed for each region. This allows us to describe qualitatively the behavior of the model in each region and to predict changes in the model dynamics as parameters are varied. In particular, we show that for some parameter values the system can exhibit long-period oscillations. A new type of dynamical behavior is also found when the system settles down either to a stationary state or to a limit cycle depending on the initial point.

Biological Clocks

Artificial neural network classification of Drosophila courtship song mutants.

Courtship songs produced by Drosophila males--wild-type, plus the cacophony and dissonance behavioral mutants--were examined with the aid of newly developed strategies for adaptive acoustic analysis and classification. This system used several techniques involving artificial neural networks (a.k.a. parallel distributed processing), including learned vector quantization of signals and non-linear adaption (back-propagation) of data analysis. "Pulse" song from several individual wild-type and mutant males were first vector-quantized according to their frequency spectra. The accumulated quantized data of this kind, for a given song, were then used to "teach" or adapt a multiple-layered feedforward artificial neural network, which classified that song according to its original genotype. Results are presented on the performance of the final adapted system when faced with novel test data and on acoustic features the system decides upon for predicting the song-mutant genotype in question. The potential applications and extensions of this new system are discussed, including how it could be used to screen for courtship mutants, search novel behavior patterns or cause-and-effect relationships associated with reproduction, compress these kinds of data for digital storage, and analyze Drosophila behavior beyond the case of courtship song.

Algorithms

Universality in neural networks: the importance of the 'mean firing rate'.

We present a general analysis of highly connected recurrent neural networks which are able to learn and retrieve a finite number of static patterns. The arguments are based on spike trains and their interval distribution and require no specific model of a neuron. In particular, they apply to formal two-state neurons as well as to more refined models like the integrate-and-fire neuron or the Hodgkin-Huxley equations. We show that the mean firing rate defined as the inverse of the mean interval length is the only relevant parameter (apart from the synaptic weights) that determines the existence of retrieval solutions with a large overlap with one of the learnt patterns. The statistics of the spiking noise (Gaussian, Poisson or other) and hence the shape of the interval distribution does not matter. Thus our unifying approach explains why, and when, all the different associative networks which treat static patterns yield basically the same results, i.e., belong to the same universality class.

Mathematics

Sensory segmentation with coupled neural oscillators.

We present a model of sensory segmentation that is based on the generation and processing of temporal tags in the form of oscillations, as suggested by the Dynamic Link Architecture. The model forms the basis for a natural solution to the sensory segmentation problem. It can deal with multiple segments, can integrate different cues and has the potential for processing hierarchical structures. Temporally tagged segments can easily be utilized in neural systems and form a natural basis for object recognition and learning. The model consists of a "cortical" circuit, an array of units that act as local feature detectors. Units are formulated as neural oscillators. Knowledge relevant to segmentation is encoded by connections. In accord with simple Gestalt laws, our concrete model has intracolumnar connections, between all units with overlapping receptive fields, and intercolumnar connections, between units responding to the same quality in different positions. An inhibitory connection system prevents total correlation and controls the grain of the segmentation. In simulations with synthetic input data we show the performance of the circuit, which produces signal correlation within segments and anticorrelation between segments.

Animals