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Animals have evolved to rapidly detect and recognize brief and intermittent encounters with odor packages, exhibiting recognition capabilities within milliseconds. Artificial olfaction has faced challenges in achieving comparable results-existing solutions are either slow; or bulky, expensive, and power-intensive-limiting applicability in real-world scenarios for mobile robotics. Here, we introduce a miniaturized high-speed electronic nose, characterized by high-bandwidth sensor readouts, tightly controlled sensing parameters, and powerful algorithms. The system is evaluated on a high-fidelity odor delivery benchmark. We showcase successful classification of tens-of-millisecond odor pulses and demonstrate temporal pattern encoding of stimuli switching with up to 60 hertz. Those timescales are unprecedented in miniaturized low-power settings and demonstrably exceed the performance observed in mice. It is now possible to match the temporal resolution of animal olfaction in robotic systems. This will allow for addressing challenges in environmental and industrial monitoring, security, neuroscience, and beyond.

In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system., Competing Interests: SB, AB, TE, IY, TR, MS, MW No competing interests declared, (© 2022, Burton et al.)

Identifying different functional regions during a brain surgery is a challenging task usually performed by highly specialized neurophysiologists. Progress in this field may be used to improve in situ brain navigation and will serve as an important building block to minimize the number of animals in preclinical brain research required by properly positioning implants intraoperatively. The study at hand aims to correlate recorded extracellular signals with the volume of origin by deep learning methods. Our work establishes connections between the position in the brain and recorded high-density neural signals. This was achieved by evaluating the performance of BLSTM, BGRU, QRNN and CNN neural network architectures on multisite electrophysiological data sets. All networks were able to successfully distinguish cortical and thalamic brain regions according to their respective neural signals. The BGRU provides the best results with an accuracy of 88.6 % and demonstrates that this classification task might be solved in higher detail while minimizing complex preprocessing steps.

Several homeostatic mechanisms enable the brain to maintain desired levels of neuronal activity. One of these, homeostatic structural plasticity, has been reported to restore activity in networks disrupted by peripheral lesions by altering their neuronal connectivity. While multiple lesion experiments have studied the changes in neurite morphology that underlie modifications of synapses in these networks, the underlying mechanisms that drive these changes are yet to be explained. Evidence suggests that neuronal activity modulates neurite morphology and may stimulate neurites to selective sprout or retract to restore network activity levels. We developed a new spiking network model of peripheral lesioning and accurately reproduced the characteristics of network repair after deafferentation that are reported in experiments to study the activity dependent growth regimes of neurites. To ensure that our simulations closely resemble the behaviour of networks in the brain, we model deafferentation in a biologically realistic balanced network model that exhibits low frequency Asynchronous Irregular (AI) activity as observed in cerebral cortex. Our simulation results indicate that the re-establishment of activity in neurons both within and outside the deprived region, the Lesion Projection Zone (LPZ), requires opposite activity dependent growth rules for excitatory and inhibitory post-synaptic elements. Analysis of these growth regimes indicates that they also contribute to the maintenance of activity levels in individual neurons. Furthermore, in our model, the directional formation of synapses that is observed in experiments requires that pre-synaptic excitatory and inhibitory elements also follow opposite growth rules. Lastly, we observe that our proposed structural plasticity growth rules and the inhibitory synaptic plasticity mechanism that also balances our AI network both contribute to the restoration of the network to pre-deafferentation stable activity levels., Competing Interests: The authors have declared that no competing interests exist.

The nervous systems converts the physical quantities sensed by its primary receptors into trains of events that are then processed in the brain. The unmatched efficiency in information processing has long inspired engineers to seek brain-like approaches to sensing and signal processing. The key principle pursued in neuromorphic sensing is to shed the traditional approach of periodic sampling in favor of an event-driven scheme that mimicks sampling as it occurs in the nervous system, where events are preferably emitted upon the change of the sensed stimulus. In this paper we highlight the advantages and challenges of event-based sensing and signal processing in the visual, auditory and olfactory domains. We also provide a survey of the literature covering neuromorphic sensing and signal processing in all three modalities. Our aim is to facilitate research in event-based sensing and signal processing by providing a comprehensive overview of the research performed previously as well as highlighting conceptual advantages, current progress and future challenges in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tayarani-Najaran and Schmuker.)

In studies of the visual system as well as in computer vision, the focus is often on contrast edges. However, the primate visual system contains a large number of cells that are insensitive to spatial contrast and, instead, respond to uniform homogeneous illumination of their visual field. The purpose of this information remains unclear. Here, we propose a mechanism that detects feature homogeneity in visual areas, based on latency coding and spike time coincidence, in a purely feed-forward and therefore rapid manner. We demonstrate how homogeneity information can interact with information on contrast edges to potentially support rapid image segmentation. Furthermore, we analyze how neuronal crosstalk (noise) affects the mechanism's performance. We show that the detrimental effects of crosstalk can be partly mitigated through delayed feed-forward inhibition that shapes bi-phasic post-synaptic events. The delay of the feed-forward inhibition allows effectively controlling the size of the temporal integration window and, thereby, the coincidence threshold. The proposed model is based on single-spike latency codes in a purely feed-forward architecture that supports low-latency processing, making it an attractive scheme of computation in spiking neuronal networks where rapid responses and low spike counts are desired.

Electronic olfaction can help detect and localize harmful gases and pollutants, but the turbulence of the natural environment presents a particular challenge: odor encounters are intermittent, and an effective electronic nose must therefore be able to resolve short odor pulses. The slow responses of the widely used metal oxide (MOX) gas sensors complicate the task. Here, we combine high-resolution data acquisition with a processing method based on Kalman filtering and absolute-deadband sampling to extract fast onset events. We find that our system can resolve the onset time of odor encounters with enough precision for source direction estimation with a pair of MOX sensors in a stereo-osmic configuration.

Cortical neurons are silent most of the time: sparse activity enables low-energy computation in the brain, and promises to do the same in neuromorphic hardware. Beyond power efficiency, sparse codes have favourable properties for associative learning, as they can store more information than local codes but are easier to read out than dense codes. Auto-encoders with a sparse constraint can learn sparse codes, and so can single-layer networks that combine recurrent inhibition with unsupervised Hebbian learning. But the latter usually require fast homeostatic plasticity, which could lead to catastrophic forgetting in embodied agents that learn continuously. Here we set out to explore whether plasticity at recurrent inhibitory synapses could take up that role instead, regulating both the population sparseness and the firing rates of individual neurons. We put the idea to the test in a network that employs compartmentalised inputs to solve the task: rate-based dendritic compartments integrate the feedforward input, while spiking integrate-and-fire somas compete through recurrent inhibition. A somato-dendritic learning rule allows somatic inhibition to modulate nonlinear Hebbian learning in the dendrites. Trained on MNIST digits and natural images, the network discovers independent components that form a sparse encoding of the input and support linear decoding. These findings confirm that intrinsic homeostatic plasticity is not strictly required for regulating sparseness: inhibitory synaptic plasticity can have the same effect. Our work illustrates the usefulness of compartmentalised inputs, and makes the case for moving beyond point neuron models in artificial spiking neural networks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.

Brains perform complex tasks using a fraction of the power that would be required to do the same on a conventional computer. New neuromorphic hardware systems are now becoming widely available that are intended to emulate the more power efficient, highly parallel operation of brains. However, to use these systems in applications, we need "neuromorphic algorithms" that can run on them. Here we develop a spiking neural network model for neuromorphic hardware that uses spike timing-dependent plasticity and lateral inhibition to perform unsupervised clustering. With this model, time-invariant, rate-coded datasets can be mapped into a feature space with a specified resolution, i.e., number of clusters, using exclusively neuromorphic hardware. We developed and tested implementations on the SpiNNaker neuromorphic system and on GPUs using the GeNN framework. We show that our neuromorphic clustering algorithm achieves results comparable to those of conventional clustering algorithms such as self-organizing maps, neural gas or k-means clustering. We then combine it with a previously reported supervised neuromorphic classifier network to demonstrate its practical use as a neuromorphic preprocessing module.

Neuromorphic computing employs models of neuronal circuits to solve computing problems. Neuromorphic hardware systems are now becoming more widely available and "neuromorphic algorithms" are being developed. As they are maturing toward deployment in general research environments, it becomes important to assess and compare them in the context of the applications they are meant to solve. This should encompass not just task performance, but also ease of implementation, speed of processing, scalability, and power efficiency. Here, we report our practical experience of implementing a bio-inspired, spiking network for multivariate classification on three different platforms: the hybrid digital/analog Spikey system, the digital spike-based SpiNNaker system, and GeNN, a meta-compiler for parallel GPU hardware. We assess performance using a standard hand-written digit classification task. We found that whilst a different implementation approach was required for each platform, classification performances remained in line. This suggests that all three implementations were able to exercise the model's ability to solve the task rather than exposing inherent platform limits, although differences emerged when capacity was approached. With respect to execution speed and power consumption, we found that for each platform a large fraction of the computing time was spent outside of the neuromorphic device, on the host machine. Time was spent in a range of combinations of preparing the model, encoding suitable input spiking data, shifting data, and decoding spike-encoded results. This is also where a large proportion of the total power was consumed, most markedly for the SpiNNaker and Spikey systems. We conclude that the simulation efficiency advantage of the assessed specialized hardware systems is easily lost in excessive host-device communication, or non-neuronal parts of the computation. These results emphasize the need to optimize the host-device communication architecture for scalability, maximum throughput, and minimum latency. Moreover, our results indicate that special attention should be paid to minimize host-device communication when designing and implementing networks for efficient neuromorphic computing.

The subjective experience of thermal pain follows the detection and encoding of noxious stimuli by primary afferent neurons called nociceptors. However, nociceptor morphology has been hard to access and the mechanisms of signal transduction remain unresolved. In order to understand how heat transducers in nociceptors are activated in vivo, it is important to estimate the temperatures that directly activate the skin-embedded nociceptor membrane. Hence, the nociceptor's temperature threshold must be estimated, which in turn will depend on the depth at which transduction happens in the skin. Since the temperature at the receptor cannot be accessed experimentally, such an estimation can currently only be achieved through modeling. However, the current state-of-the-art model to estimate temperature at the receptor suffers from the fact that it cannot account for the natural stochastic variability of neuronal responses. We improve this model using a probabilistic approach which accounts for uncertainties and potential noise in system. Using a data set of 24 C-fibers recorded in vitro, we show that, even without detailed knowledge of the bio-thermal properties of the system, the probabilistic model that we propose here is capable of providing estimates of threshold and depth in cases where the classical method fails.

To internally reflect the sensory environment, animals create neural maps encoding the external stimulus space. From that primary neural code relevant information has to be extracted for accurate navigation. We analyzed how different odor features such as hedonic valence and intensity are functionally integrated in the lateral horn (LH) of the vinegar fly, Drosophila melanogaster. We characterized an olfactory-processing pathway, comprised of inhibitory projection neurons (iPNs) that target the LH exclusively, at morphological, functional and behavioral levels. We demonstrate that iPNs are subdivided into two morphological groups encoding positive hedonic valence or intensity information and conveying these features into separate domains in the LH. Silencing iPNs severely diminished flies' attraction behavior. Moreover, functional imaging disclosed a LH region tuned to repulsive odors comprised exclusively of third-order neurons. We provide evidence for a feature-based map in the LH, and elucidate its role as the center for integrating behaviorally relevant olfactory information.

Segmentation of functional parts in image series of functional activity is a common problem in neuroscience. Here we apply regularized non-negative matrix factorization (rNMF) to extract glomeruli in intrinsic optical signal (IOS) images of the olfactory bulb. Regularization allows us to incorporate prior knowledge about the spatio-temporal characteristics of glomerular signals. We demonstrate how to identify suitable regularization parameters on a surrogate dataset. With appropriate regularization segmentation by rNMF is more resilient to noise and requires fewer observations than conventional spatial independent component analysis (sICA). We validate our approach in experimental data using anatomical outlines of glomeruli obtained by 2-photon imaging of resting synapto-pHluorin fluorescence. Taken together, we show that rNMF provides a straightforward method for problem tailored source separation that enables reliable automatic segmentation of functional neural images, with particular benefit in situations with low signal-to-noise ratio as in IOS imaging., (Copyright © 2014. Published by Elsevier Inc.)

Computational neuroscience has uncovered a number of computational principles used by nervous systems. At the same time, neuromorphic hardware has matured to a state where fast silicon implementations of complex neural networks have become feasible. En route to future technical applications of neuromorphic computing the current challenge lies in the identification and implementation of functional brain algorithms. Taking inspiration from the olfactory system of insects, we constructed a spiking neural network for the classification of multivariate data, a common problem in signal and data analysis. In this model, real-valued multivariate data are converted into spike trains using "virtual receptors" (VRs). Their output is processed by lateral inhibition and drives a winner-take-all circuit that supports supervised learning. VRs are conveniently implemented in software, whereas the lateral inhibition and classification stages run on accelerated neuromorphic hardware. When trained and tested on real-world datasets, we find that the classification performance is on par with a naïve Bayes classifier. An analysis of the network dynamics shows that stable decisions in output neuron populations are reached within less than 100 ms of biological time, matching the time-to-decision reported for the insect nervous system. Through leveraging a population code, the network tolerates the variability of neuronal transfer functions and trial-to-trial variation that is inevitably present on the hardware system. Our work provides a proof of principle for the successful implementation of a functional spiking neural network on a configurable neuromorphic hardware system that can readily be applied to real-world computing problems.

Responses of olfactory receptors (ORs) can be predicted by applying machine learning methods on a multivariate encoding of an odorant's chemical structure. Physicochemical descriptors that encode features of the molecular graph are a popular choice for such an encoding. Here, we explore the EVA descriptor set, which encodes features derived from the vibrational spectrum of a molecule. We assessed the performance of Support Vector Regression (SVR) and Random Forest Regression (RFR) to predict the gradual response of Drosophila ORs. We compared a 27-dimensional variant of the EVA descriptor against a set of 1467 descriptors provided by the eDragon software package, and against a 32-dimensional subset thereof that has been proposed as the basis for an odor metric consisting of 32 descriptors (HADDAD). The best prediction performance was reproducibly achieved using SVR on the highest-dimensional feature set. The low-dimensional EVA and HADDAD feature sets predicted odor-OR interactions with similar accuracy. Adding charge and polarizability information to the EVA descriptor did not improve the results but rather decreased predictive power. Post-hoc in vivo measurements confirmed these results. Our findings indicate that EVA provides a meaningful low-dimensional representation of odor space, although EVA hardly outperformed "classical" descriptor sets., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, we present a highly configurable neuromorphic computing substrate and use it for emulating several types of neural networks. At the heart of this system lies a mixed-signal chip, with analog implementations of neurons and synapses and digital transmission of action potentials. Major advantages of this emulation device, which has been explicitly designed as a universal neural network emulator, are its inherent parallelism and high acceleration factor compared to conventional computers. Its configurability allows the realization of almost arbitrary network topologies and the use of widely varied neuronal and synaptic parameters. Fixed-pattern noise inherent to analog circuitry is reduced by calibration routines. An integrated development environment allows neuroscientists to operate the device without any prior knowledge of neuromorphic circuit design. As a showcase for the capabilities of the system, we describe the successful emulation of six different neural networks which cover a broad spectrum of both structure and functionality.

The honeybee Apis mellifera has a remarkable ability to detect and locate food sources during foraging, and to associate odor cues with food rewards. In the honeybee's olfactory system, sensory input is first processed in the antennal lobe (AL) network. Uniglomerular projection neurons (PNs) convey the sensory code from the AL to higher brain regions via two parallel but anatomically distinct pathways, the lateral and the medial antenno-cerebral tract (l- and m-ACT). Neurons innervating either tract show characteristic differences in odor selectivity, concentration dependence, and representation of mixtures. It is still unknown how this differential stimulus representation is achieved within the AL network. In this contribution, we use a computational network model to demonstrate that the experimentally observed features of odor coding in PNs can be reproduced by varying lateral inhibition and gain control in an otherwise unchanged AL network. We show that odor coding in the l-ACT supports detection and accurate identification of weak odor traces at the expense of concentration sensitivity, while odor coding in the m-ACT provides the basis for the computation and following of concentration gradients but provides weaker discrimination power. Both coding strategies are mutually exclusive, which creates a tradeoff between detection accuracy and sensitivity. The development of two parallel systems may thus reflect an evolutionary solution to this problem that enables honeybees to achieve both tasks during bee foraging in their natural environment, and which could inspire the development of artificial chemosensory devices for odor-guided navigation in robots.

How are odor mixtures perceived? We take a behavioral approach toward this question, using associative odor-recognition experiments in Drosophila. We test how strongly flies avoid a binary mixture after punishment training with one of its constituent elements and how much, in turn, flies avoid an odor element if it had been a component of a previously punished binary mixture. A distinguishing feature of our approach is that we first adjust odors for task-relevant behavioral potency, that is, for equal learnability. Doing so, we find that 1) generalization between mixture and elements is symmetrical and partial, 2) elements are equally similar to all mixtures containing it and that 3) mixtures are equally similar to both their constituent elements. As boundary conditions for the applicability of these rules, we note that first, although variations in learnability are small and remain below statistical cut-off, these variations nevertheless correlate with the elements' perceptual "weight" in the mixture; thus, even small differences in learnability between the elements have the potential to feign mixture asymmetries. Second, the more distant the elements of a mixture are to each other in terms of their physicochemical properties, the more distant the flies regard the elements from the mixture. Thus, titrating for task-relevant behavioral potency and taking into account physicochemical relatedness of odors reveals rules of mixture perception that, maybe surprisingly, appear to be fairly simple.

An important component in understanding central olfactory processing and coding in the insect brain relates to the characterization of the functional divisions between morphologically distinct types of projection neurons (PN). Using calcium imaging, we investigated how the identity, concentration and mixtures of odors are represented in axon terminals (boutons) of two types of PNs - lPN and mPN. In lPN boutons we found less concentration dependence, narrow tuning profiles at a high concentration, which may be optimized for fine, concentration-invariant odor discrimination. In mPN boutons, however, we found clear rising concentration dependence, broader tuning profiles at a high concentration, which may be optimized for concentration coding. In addition, we found more mixture suppression in lPNs than in mPNs, indicating lPNs better adaptation for synthetic mixture processing. These results suggest a functional division of odor processing in both PN types.

The chemical sense of insects has evolved to encode and classify odorants. Thus, the neural circuits in their olfactory system are likely to implement an efficient method for coding, processing, and classifying chemical information. Here, we describe a computational method to process molecular representations and classify molecules. The three-step approach mimics neurocomputational principles observed in olfactory systems. In the first step, the original stimulus space is sampled by "virtual receptors," which are chemotopically arranged by a self-organizing map. In the second step, the signals from the virtual receptors are decorrelated via correlation-based lateral inhibition. Finally, in the third step, olfactory scent perception is modeled by a machine learning classifier. We found that signal decorrelation during the second stage significantly increases the accuracy of odorant classification. Moreover, our results suggest that the proposed signal transform is capable of dimensionality reduction and is more robust against overdetermined representations than principal component scores. Our olfaction-inspired method was successfully applied to predicting bioactivities of pharmaceutically active compounds with high accuracy. It represents a way to efficiently connect chemical structure with biological activity space.

Background: Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way., Results: We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation., Conclusion: The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their "receptive fields". Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data.

SOMMER is a publicly available, Java-based toolbox for training and visualizing two- and three-dimensional unsupervised self-organizing maps (SOMs). Various map topologies are implemented for planar rectangular, toroidal, cubic-surface and spherical projections. The software allows for visualization of the training process, which has been shown to be particularly valuable for teaching purposes.

Background: Particle Swarm Optimization (PSO) is an established method for parameter optimization. It represents a population-based adaptive optimization technique that is influenced by several "strategy parameters". Choosing reasonable parameter values for the PSO is crucial for its convergence behavior, and depends on the optimization task. We present a method for parameter meta-optimization based on PSO and its application to neural network training. The concept of the Optimized Particle Swarm Optimization (OPSO) is to optimize the free parameters of the PSO by having swarms within a swarm. We assessed the performance of the OPSO method on a set of five artificial fitness functions and compared it to the performance of two popular PSO implementations., Results: Our results indicate that PSO performance can be improved if meta-optimized parameter sets are applied. In addition, we could improve optimization speed and quality on the other PSO methods in the majority of our experiments. We applied the OPSO method to neural network training with the aim to build a quantitative model for predicting blood-brain barrier permeation of small organic molecules. On average, training time decreased by a factor of four and two in comparison to the other PSO methods, respectively. By applying the OPSO method, a prediction model showing good correlation with training-, test- and validation data was obtained., Conclusion: Optimizing the free parameters of the PSO method can result in performance gain. The OPSO approach yields parameter combinations improving overall optimization performance. Its conceptual simplicity makes implementing the method a straightforward task.

Besides the choice of an automated software method for selecting 'maximally diverse' compounds from a large pool of molecules, it is the implementation of the algorithm that critically determines the usefulness of the approach. The speed of execution of two implementations of the Maxmin algorithm is compared for the selection of maximally diverse subsets of large compound collections. Different versions of the software are compared using various C compiler options and Java virtual machines. The analysis shows that the Maxmin algorithm can be implemented in both languages yielding sufficient speed of execution. For large compound libraries the Java version outperformes the C version. While the Java version selects the same compounds independent of the virtual machine used, the C version produces slightly different subsets depending on the compiler and on the optimization settings.

The malaria causing protozoan Plasmodium falciparum contains a vestigal, non-photosynthetic plastid, the apicoplast. Numerous proteins encoded by nuclear genes are targeted to the apicoplast courtesy of N-terminal extensions. With the impending sequence completion of an entire genome of the malaria parasite, it is important to have software tools in place for prediction of subcellular locations for all proteins. Apicoplast targeting signals are bipartite; containing a signal peptide and a transit peptide. Nuclear-encoded apicoplast protein precursors were analyzed for characteristic features by statistical methods, principal component analysis, self-organizing maps, and supervised neural networks. The transit peptide contains a net positive charge and is rich in asparagine, lysine, and isoleucine residues. A novel prediction system (PATS, predict apicoplast-targeted sequences) was developed based on various sequence features, yielding a Matthews correlation coefficient of 0.91 (97% correct predictions) in a 40-fold cross-validation study. This system predicted 22% apicoplast proteins of the 205 potential proteins on P. falciparum chromosome 2, and 21% of 243 chromosome 3 proteins. A combination of the PATS results with a signal peptide prediction yields 15% potentially nuclear-encoded apicoplast proteins on chromosomes 2 and 3. The prediction tool will advance P. falciparum genome analysis, and it might help to identify apicoplast proteins as drug targets for the development of novel anti-malaria agents.