Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks

Gene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data

A Logistic Model Tree Solution

Beretta, S., Castelli, M., Gonçalves, I., Kel, I., Giansanti, V., & Merelli, I. (2018). Improving eQTL Analysis Using a Machine Learning Approach for Data Integration: A Logistic Model Tree Solution. Journal of Computational Biology, 25(10), 1091-1105. DOI: 10.1089/cmb.2017.0167Expression quantitative trait loci (eQTL) analysis is an emerging method for establishing the impact of genetic variations (such as single nucleotide polymorphisms) on the expression levels of genes. Although different methods for evaluating the impact of these variations are proposed in the literature, the results obtained are mostly in disagreement, entailing a considerable number of false-positive predictions. For this reason, we propose an approach based on Logistic Model Trees that integrates the predictions of different eQTL mapping tools to produce more reliable results. More precisely, we employ a machine learning-based method using logistic functions to perform a linear regression able to classify the predictions of three eQTL analysis tools (namely, R/qtl, MatrixEQTL, and mRMR). Given the lack of a reference dataset and that computational predictions are not so easy to test experimentally, the performance of our approach is assessed using data from the DREAM5 challenge. The results show the quality of the aggregated prediction is better than that obtained by each single tool in terms of both precision and recall. We also performed a test on real data, employing genotypes and microRNA expression profiles from Caenorhabditis elegans, which proved that we were able to correctly classify all the experimentally validated eQTLs. These good results come both from the integration of the different predictions, and from the ability of this machine learning algorithm to find the best cutoff thresholds for each tool. This combination makes our integration approach suitable for improving eQTL predictions for testing in a laboratory, reducing the number of false-positive results.authorsversionpublishe

Early Classification of Pathological Heartbeats on Wireless Body Sensor Nodes

Smart Wireless Body Sensor Nodes (WBSNs) are a novel class of unobtrusive, battery-powered devices allowing the continuous monitoring and real-time interpretation of a subject's bio-signals, such as the electrocardiogram (ECG). These low-power platforms, while able to perform advanced signal processing to extract information on heart conditions, are usually constrained in terms of computational power and transmission bandwidth. It is therefore essential to identify in the early stages which parts of an ECG are critical for the diagnosis and, only in these cases, activate on demand more detailed and computationally intensive analysis algorithms. In this work, we present a comprehensive framework for real-time automatic classification of normal and abnormal heartbeats, targeting embedded and resource-constrained WBSNs. In particular, we provide a comparative analysis of different strategies to reduce the heartbeat representation dimensionality, and therefore the required computational effort. We then combine these techniques with a neuro-fuzzy classification strategy, which effectively discerns normal and pathological heartbeats with a minimal run time and memory overhead. We prove that, by performing a detailed analysis only on the heartbeats that our classifier identifies as abnormal, a WBSN system can drastically reduce its overall energy consumption. Finally, we assess the choice of neuro-fuzzy classification by comparing its performance and workload with respect to other state-of-the-art strategies. Experimental results using the MIT-BIH Arrhythmia database show energy savings of as much as 60% in the signal processing stage, and 63% in the subsequent wireless transmission, when a neuro-fuzzy classification structure is employed, coupled with a dimensionality reduction technique based on random projections

537. New Graph-Based Algorithm for Comprehensive Identification and Tracking Retroviral Integration Sites

Vector integration sites (IS) in hematopoietic stem cell (HSC) gene therapy (GT) applications are stable genetic marks, distinctive for each independent cell clone and its progeny. The characterization of IS allows to identify each cell clone and individually track its fate in different tissues or cell lineages and during time, and is required for assessing the safety and efficacy of the treatment. Bioinformatics pipelines for IS detection used in GT identify the sequence reads mapping in the same genomic position of the reference genome as a single IS but discard those ambiguously mapped in multiple genomic regions. The loss of such significant portion of patients' IS may hide potential malignant events thus reducing the reliability of IS studies. We developed a novel tool that is able to accurately identify IS in any genomic region even if composed by repetitive genomic sequences. Our approach exploits an initial genome free analysis of sequencing reads by creating an undirected graph in which nodes are the input sequences and edges represent valid alignments (over a specific identity threshold) between pairs of nodes. Through the analysis and decomposition of the graph, the method identifies indivisible subgraphs of sequences (clusters), each of them corresponding to an IS. Once extracted the consensus sequence of the clusters and aligned on the reference genome, we collect the alignment results and the annotation labels from RepeatMasker. By combining the set of genomic coordinates and the annotation labels, the method retraces the initial sequence graph, statistically validates the clusters through permutation test and produces the final list of IS. We tested the reliability of our tool on 3 IS datasets generated from simulated sequencing reads with incremental rate of nucleotide variations (0%, 0.25% and 0.5%) and real data from a cell line with known IS and we compared out tool to VISPA and UClust, used for GT studies. In the simulated datasets our tool demonstrated precision and recall ranging 0.85-0.97 and 0.88-0.99 respectively, producing the aggregate F-score ranging 0.86-0.98 which resulted higher than VISPA and UClust. In the experimental case of sequences from LAM-PCR products, our tool and VISPA were able to identify all the 6 known ISs for >98% of the reads produced, while UClust identified only 5 out 6 ISs. We then used our tool to reanalyze the sequencing reads of our GT clinical trial for Metachromatic Leukodystrophy (MLD) completing the hidden portion of IS. The overall number of ISs, sequencing reads and estimated actively re-populating HSCs was increased by an average fold ~1.5 with respect the previously published data obtained through VISPA whereas the diversity index of the population did not change and no aberrant clones in repeats occurred. Our tool addresses and solves important open issues in retroviral IS identification and clonal tracking, allowing the generation of a comprehensive repertoire of IS

Hardware/Software Approach for Code Synchronization in Low-Power Multi-Core Sensor Nodes

Latest embedded bio-signal analysis applications, targeting low-power Wireless Body Sensor Nodes (WBSNs), present conflicting requirements. On one hand, bio-signal analysis applications are continuously increasing their demand for high computing capabilities. On the other hand, long-term signal processing in WBSNs must be provided within their highly constrained energy budget. In this context, parallel processing effectively increases the power efficiency of WBSNs, but only if the execution can be properly synchronized among computing elements. To address this challenge, in this work we propose a hardware/software approach to synchronize the execution of bio-signal processing applications in multi-core WBSNs. This new approach requires little hardware resources and very few adaptations in the source code. Moreover, it provides the necessary flexibility to execute applications with an arbitrarily large degree of complexity and parallelism, enabling considerable reductions in power consumption for all multi-core WBSN execution conditions. Experimental results show that a multi-core WBSN architecture using the illustrated approach can obtain energy savings of up to 40%, with respect to an equivalent singlecore architecture, when performing advanced bio-signal analysi

Design Methods for Parallel Hardware Implementation of Multimedia Iterative Algorithms

Traditionally, parallel implementations of multimedia algorithms are carried out manually, since the automation of this task is very difficult due to the complex dependencies that generally exist between different elements of the data set. Moreover, there is a wide family of iterative multimedia algorithms that cannot be executed with satisfactory performance on Multi-Processor Systems-on-Chip or Graphics Processing Units. For this reason, new methods to design custom hardware circuits that exploit the intrinsic parallelism of multimedia algorithms are needed. As a consequence, in this paper, we propose a novel design method for the definition of hardware systems optimized for a particular class of multimedia iterative algorithms. We have successfully applied the proposed approach to several real-world case studies, such as iterative convolution filters and the Chambolle algorithm, and the proposed design method has been able to automatically implement, for each one of them, a parallel architecture able to meet real-time performance (up to 72 frames per second for the Chambolle algorithm), with on-chip memory requirements from 2 to 3 orders of magnitude smaller than the state-of-the art approaches

A High–Performance Parallel Implementation of the Chambolle Algorithm

The determination of the optical flow is a central problem in image processing, as it allows to describe how an image changes over time by means of a numerical vector field. The estimation of the optical flow is however a very complex problem, which has been faced using many different mathematical approaches. A large body of work has been recently published about variational methods, following the technique for total variation minimization proposed by Chambolle. Still, their hardware implementations do not offer good performances in terms of frames that can be processed per time unit, mainly because of the complex dependency scheme among the data. In this work, we propose a highly parallel and accelerated FPGA implementation of the Chambolle algorithm, which splits the original image into a set of overlapping sub-frames and efficiently exploits the reuse of intermediate results. We validate our hardware on large frames (up to 1024 × 768), and the proposed approach largely outperforms the state-of-the-art implementations, reaching up to 76× speedups as well as realtime frame rates even at high resolutions

A Wireless Body Sensor Network For Activity Monitoring With Low Transmission Overhead

Activity recognition has been a research field of high interest over the last years, and it finds application in the medical domain, as well as personal healthcare monitoring during daily home- and sports-activities. With the aim of producing minimum discomfort while performing supervision of subjects, miniaturized networks of low-power wireless nodes are typically deployed on the body to gather and transmit physiological data, thus forming a Wireless Body Sensor Network (WBSN). In this work, we propose a WBSN for online activity monitoring, which combines the sensing capabilities of wearable nodes and the high computational resources of modern smartphones. The proposed solution provides different tradeoffs between classification accuracy and energy consumption, thanks to different workloads assigned to the nodes and to the mobile phone in different network configurations. In particular, our WBSN is able to achieve very high activity recognition accuracies (up to 97.2%) on multiple subjects, while significantly reducing the sampling frequency and the volume of transmitted data with respect to other state-of-the art solutions

Model-Based Design for Wireless Body Sensor Network Nodes

Wireless body sensor networks (WBSNs) are a rising technology that allows constant and unobtrusive monitoring of the vital signals of a patient. The configuration of a WBSN node proves to be critical in order to maximize its lifetime, while meeting the predefined performance during signal sensing, preprocessing, and wireless transmission to the base station. In this work, we propose a model-based optimization framework for WBSN nodes, which is centered on a detailed analytical characterization of the most energy-demanding components of this application domain. We also propose a multi-objective exploration algorithm to evaluate the node configurations and the corresponding performance tradeoffs. A case study is discussed to validate the proposed framework, proving that our model captures the behavior of real WBSNs and efficiently leads to the determination of the Pareto-optimal configurations