On the Use of Topological Features of Metabolic Networks for the Classification of Cancer Samples.

BACKGROUND: The increasing availability of omics data collected from patients affected by severe pathologies, such as cancer, is fostering the development of data science methods for their analysis. INTRODUCTION: The combination of data integration and machine learning approaches can provide new powerful instruments to tackle the complexity of cancer development and deliver effective diagnostic and prognostic strategies. METHODS: We explore the possibility of exploiting the topological properties of sample-specific metabolic networks as features in a supervised classification task. Such networks are obtained by projecting transcriptomic data from RNA-seq experiments on genome-wide metabolic models to define weighted networks modeling the overall metabolic activity of a given sample. RESULTS: We show the classification results on a labeled breast cancer dataset from the TCGA database, including 210 samples (cancer vs. normal). In particular, we investigate how the performance is affected by a threshold-based pruning of the networks by comparing Artificial Neural Networks, Support Vector Machines and Random Forests. Interestingly, the best classification performance is achieved within a small threshold range for all methods, suggesting that it might represent an effective choice to recover useful information while filtering out noise from data. Overall, the best accuracy is achieved with SVMs, which exhibit performances similar to those obtained when gene expression profiles are used as features. CONCLUSION: These findings demonstrate that the topological properties of sample-specific metabolic networks are effective in classifying cancer and normal samples, suggesting that useful information can be extracted from a relatively limited number of features.

Social interaction layers in complex networks for the dynamical epidemic modeling of COVID-19 in Brazil.

We are currently living in a state of uncertainty due to the pandemic caused by the SARS-CoV-2 virus. There are several factors involved in the epidemic spreading, such as the individual characteristics of each city/country. The true shape of the epidemic dynamics is a large, complex system, considerably hard to predict. In this context, Complex networks are a great candidate for analyzing these systems due to their ability to tackle structural and dynamic properties. Therefore, this study presents a new approach to model the COVID-19 epidemic using a multi-layer complex network, where nodes represent people, edges are social contacts, and layers represent different social activities. The model improves the traditional SIR, and it is applied to study the Brazilian epidemic considering data up to 05/26/2020, and analyzing possible future actions and their consequences. The network is characterized using statistics of infection, death, and hospitalization time. To simulate isolation, social distancing, or precautionary measures, we remove layers and reduce social contact's intensity. Results show that even taking various optimistic assumptions, the current isolation levels in Brazil still may lead to a critical scenario for the healthcare system and a considerable death toll (average of 149,000). If all activities return to normal, the epidemic growth may suffer a steep increase, and the demand for ICU beds may surpass three times the country's capacity. This situation would surely lead to a catastrophic scenario, as our estimation reaches an average of 212,000 deaths, even considering that all cases are effectively treated. The increase of isolation (up to a lockdown) shows to be the best option to keep the situation under the healthcare system capacity, aside from ensuring a faster decrease of new case occurrences (months of difference), and a significantly smaller death toll (average of 87,000).

Electrochemical and optical detection and machine learning applied to images of genosensors for diagnosis of prostate cancer with the biomarker PCA3.

The development of simple detection methods aimed at widespread screening and testing is crucial for many infections and diseases, including prostate cancer where early diagnosis increases the chances of cure considerably. In this paper, we report on genosensors with different detection principles for a prostate cancer specific DNA sequence (PCA3). The genosensors were made with carbon printed electrodes or quartz coated with layer-by-layer (LbL) films containing gold nanoparticles and chondroitin sulfate and a layer of a complementary DNA sequence (PCA3 probe). The highest sensitivity was reached with electrochemical impedance spectroscopy with the detection limit of 83 pM in solutions of PCA3, while the limits of detection were 2000 pM and 900 pM for cyclic voltammetry and UV-vis spectroscopy, respectively. That detection could be performed with an optical method is encouraging, as one may envisage extending it to colorimetric tests. Since the morphology of sensing units is known to be affected in detection experiments, we applied machine learning algorithms to classify scanning electron microscopy images of the genosensors and managed to distinguish those exposed to PCA3-containing solutions from control measurements with an accuracy of 99.9%. The performance in distinguishing each individual PCA3 concentration in a multiclass task was lower, with an accuracy of 88.3%, which means that further developments in image analysis are required for this innovative approach.

Automatic Stomatal Segmentation Based on Delaunay-Rayleigh Frequency Distance.

The CO2 and water vapor exchange between leaf and atmosphere are relevant for plant physiology. This process is done through the stomata. These structures are fundamental in the study of plants since their properties are linked to the evolutionary process of the plant, as well as its environmental and phytohormonal conditions. Stomatal detection is a complex task due to the noise and morphology of the microscopic images. Although in recent years segmentation algorithms have been developed that automate this process, they all use techniques that explore chromatic characteristics. This research explores a unique feature in plants, which corresponds to the stomatal spatial distribution within the leaf structure. Unlike segmentation techniques based on deep learning tools, we emphasize the search for an optimal threshold level, so that a high percentage of stomata can be detected, independent of the size and shape of the stomata. This last feature has not been reported in the literature, except for those results of geometric structure formation in the salt formation and other biological formations.

Real-time prediction of influenza outbreaks in Belgium.

Seasonal influenza is a worldwide public health concern. Forecasting its dynamics can improve the management of public health regulations, resources and infrastructure, and eventually reduce mortality and the costs induced by influenza-related absenteism. In Belgium, a network of Sentinel General Practitioners (SGPs) is in place for the early detection of the seasonal influenza epidemic. This surveillance network reports the weekly incidence of influenza-like illness (ILI) cases, which makes it possible to detect the epidemic onset, as well as other characteristics of the epidemic season. In this paper, we present an approach for predicting the weekly ILI incidence in real-time by resorting to a dynamically calibrated compartmental model, which furthermore takes into account the dynamics of other influenza seasons. In order to validate the proposed approach, we used data collected by the Belgian SGPs for the influenza seasons 2010-2016. In spite of the great variability among different epidemic seasons, providing weekly predictions makes it possible to capture variations in the ILI incidence. The confidence region becomes more representative of the epidemic behavior as ILI data from more seasons become available. Since the SIR model is then calibrated dynamically every week, the predicted ILI curve gets rapidly tuned to the dynamics of the ongoing season. The results show that the proposed method can be used to characterize the overall behavior of an epidemic.

Clustering algorithms: A comparative approach.

Many real-world systems can be studied in terms of pattern recognition tasks, so that proper use (and understanding) of machine learning methods in practical applications becomes essential. While many classification methods have been proposed, there is no consensus on which methods are more suitable for a given dataset. As a consequence, it is important to comprehensively compare methods in many possible scenarios. In this context, we performed a systematic comparison of 9 well-known clustering methods available in the R language assuming normally distributed data. In order to account for the many possible variations of data, we considered artificial datasets with several tunable properties (number of classes, separation between classes, etc). In addition, we also evaluated the sensitivity of the clustering methods with regard to their parameters configuration. The results revealed that, when considering the default configurations of the adopted methods, the spectral approach tended to present particularly good performance. We also found that the default configuration of the adopted implementations was not always accurate. In these cases, a simple approach based on random selection of parameters values proved to be a good alternative to improve the performance. All in all, the reported approach provides subsidies guiding the choice of clustering algorithms.

Topological assessment of metabolic networks reveals evolutionary information.

Evolutionary information was inferred from the topology of metabolic networks corresponding to 17 plant species belonging to major plant lineages Chlorophytes, Bryophytes, Lycophytes and Angiosperms. The plant metabolic networks were built using the substrate-product network modeling based on the metabolic reactions available on the PlantCyc database (version 9.5), from which their local topological properties such as degree, in-degree, out-degree, clustering coefficient, hub-score, authority-score, local efficiency, betweenness and eigencentrality were measured. The topological measurements corresponding to each metabolite within the networks were considered as a set of metabolic characters to compound a feature vector representing each plant. Our results revealed that some local topological characters are able to discern among plant kinships, since similar phylogenies were found when comparing dendrograms obtained by topological metrics to the one obtained by DNA sequences of chloroplast genes. Furthermore, we also found that even a smaller number of metabolic characters is able to separate among major clades with high bootstrap support (BS > 95), while for some suborders a bigger content has been required.

A hierarchical model of metabolic machinery based on the kcore decomposition of plant metabolic networks.

Modeling the basic structure of metabolic machinery is a challenge for modern biology. Some models based on complex networks have provided important information regarding this machinery. In this paper, we constructed metabolic networks of 17 plants covering unicellular organisms to more complex dicotyledonous plants. The metabolic networks were built based on the substrate-product model and a topological percolation was performed using the kcore decomposition. The distribution of metabolites across the percolation layers showed correlations between the metabolic integration hierarchy and the network topology. We show that metabolites concentrated in the internal network (maximum kcore) only comprise molecules of the primary basal metabolism. Moreover, we found a high proportion of a set of common metabolites, among the 17 plants, centered at the inner kcore layers. Meanwhile, the metabolites recognized as participants in the secondary metabolism of plants are concentrated in the outermost layers of the network. This data suggests that the metabolites in the central layer form a basic molecular module in which the whole plant metabolism is anchored. The elements from this central core participate in almost all plant metabolic reactions, which suggests that plant metabolic networks follows a centralized topology.

Authorship attribution based on Life-Like Network Automata.

The authorship attribution is a problem of considerable practical and technical interest. Several methods have been designed to infer the authorship of disputed documents in multiple contexts. While traditional statistical methods based solely on word counts and related measurements have provided a simple, yet effective solution in particular cases; they are prone to manipulation. Recently, texts have been successfully modeled as networks, where words are represented by nodes linked according to textual similarity measurements. Such models are useful to identify informative topological patterns for the authorship recognition task. However, there is no consensus on which measurements should be used. Thus, we proposed a novel method to characterize text networks, by considering both topological and dynamical aspects of networks. Using concepts and methods from cellular automata theory, we devised a strategy to grasp informative spatio-temporal patterns from this model. Our experiments revealed an outperformance over structural analysis relying only on topological measurements, such as clustering coefficient, betweenness and shortest paths. The optimized results obtained here pave the way for a better characterization of textual networks.

Improving the pseudo-randomness properties of chaotic maps using deep-zoom.

A generalized method is proposed to compose new orbits from a given chaotic map. The method provides an approach to examine discrete-time chaotic maps in a "deep-zoom" manner by using k-digits to the right from the decimal separator of a given point from the underlying chaotic map. Interesting phenomena have been identified. Rapid randomization was observed, i.e., chaotic patterns tend to become indistinguishable when compared to the original orbits of the underlying chaotic map. Our results were presented using different graphical analyses (i.e., time-evolution, bifurcation diagram, Lyapunov exponent, Poincaré diagram, and frequency distribution). Moreover, taking advantage of this randomization improvement, we propose a Pseudo-Random Number Generator (PRNG) based on the k-logistic map. The pseudo-random qualities of the proposed PRNG passed both tests successfully, i.e., DIEHARD and NIST, and were comparable with other traditional PRNGs such as the Mersenne Twister. The results suggest that simple maps such as the logistic map can be considered as good PRNG methods.

Morphological classification of odontogenic keratocysts using Bouligand-Minkowski fractal descriptors.

The Odontogenic keratocyst (OKC) is a cystic lesion of the jaws, which has high growth and recurrence rates compared to other cysts of the jaws (for instance, radicular cyst, which is the most common jaw cyst type). For this reason OKCs are considered by some to be benign neoplasms. There exist two sub-types of OKCs (sporadic and syndromic) and the ability to discriminate between these sub-types, as well as other jaw cysts, is an important task in terms of disease diagnosis and prognosis. With the development of digital pathology, computational algorithms have become central to addressing this type of problem. Considering that only basic feature-based methods have been investigated in this problem before, we propose to use a different approach (the Bouligand-Minkowski descriptors) to assess the success rates achieved on the classification of a database of histological images of the epithelial lining of these cysts. This does not require the level of abstraction necessary to extract histologically-relevant features and therefore has the potential of being more robust than previous approaches. The descriptors were obtained by mapping pixel intensities into a three dimensional cloud of points in discrete space and applying morphological dilations with spheres of increasing radii. The descriptors were computed from the volume of the dilated set and submitted to a machine learning algorithm to classify the samples into diagnostic groups. This approach was capable of discriminating between OKCs and radicular cysts in 98% of images (100% of cases) and between the two sub-types of OKCs in 68% of images (71% of cases). These results improve over previously reported classification rates reported elsewhere and suggest that Bouligand-Minkowski descriptors are useful features to be used in histopathological images of these cysts.

Shape analysis using fractal dimension: a curvature based approach.

The present work shows a novel fractal dimension method for shape analysis. The proposed technique extracts descriptors from a shape by applying a multi-scale approach to the calculus of the fractal dimension. The fractal dimension is estimated by applying the curvature scale-space technique to the original shape. By applying a multi-scale transform to the calculus, we obtain a set of descriptors which is capable of describing the shape under investigation with high precision. We validate the computed descriptors in a classification process. The results demonstrate that the novel technique provides highly reliable descriptors, confirming the efficiency of the proposed method.