1,655 research outputs found

    The AddACO: A bio-inspired modified version of the ant colony optimization algorithm to solve travel salesman problems

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    The Travel Salesman Problem (TSP) consists in finding the minimal-length closed tour that connects the entire group of nodes of a given graph. We propose to solve such a combinatorial optimization problem with the AddACO algorithm: it is a version of the Ant Colony Optimization method that is characterized by a modified probabilistic law at the basis of the exploratory movement of the artificial insects. In particular, the ant decisional rule is here set to amount in a linear convex combination of competing behavioral stimuli and has therefore an additive form (hence the name of our algorithm), rather than the canonical multiplicative one. The AddACO intends to address two conceptual shortcomings that characterize classical ACO methods: (i) the population of artificial insects is in principle allowed to simultaneously minimize/maximize all migratory guidance cues (which is in implausible from a biological/ecological point of view) and (ii) a given edge of the graph has a null probability to be explored if at least one of the movement trait is therein equal to zero, i.e., regardless the intensity of the others (this in principle reduces the exploratory potential of the ant colony). Three possible variants of our method are then specified: the AddACO-V1, which includes pheromone trail and visibility as insect decisional variables, and the AddACO-V2 and the AddACO-V3, which in turn add random effects and inertia, respectively, to the two classical migratory stimuli. The three versions of our algorithm are tested on benchmark middle-scale TPS instances, in order to assess their performance and to find their optimal parameter setting. The best performing variant is finally applied to large-scale TSPs, compared to the naive Ant-Cycle Ant System, proposed by Dorigo and colleagues, and evaluated in terms of quality of the solutions, computational time, and convergence speed. The aim is in fact to show that the proposed transition probability, as long as its conceptual advantages, is competitive from a performance perspective, i.e., if it does not reduce the exploratory capacity of the ant population w.r.t. the canonical one (at least in the case of selected TSPs). A theoretical study of the asymptotic behavior of the AddACO is given in the appendix of the work, whose conclusive section contains some hints for further improvements of our algorithm, also in the perspective of its application to other optimization problems

    Data- og ekspertdreven variabelseleksjon for prediktive modeller i helsevesenet : mot økt tolkbarhet i underbestemte maskinlæringsproblemer

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    Modern data acquisition techniques in healthcare generate large collections of data from multiple sources, such as novel diagnosis and treatment methodologies. Some concrete examples are electronic healthcare record systems, genomics, and medical images. This leads to situations with often unstructured, high-dimensional heterogeneous patient cohort data where classical statistical methods may not be sufficient for optimal utilization of the data and informed decision-making. Instead, investigating such data structures with modern machine learning techniques promises to improve the understanding of patient health issues and may provide a better platform for informed decision-making by clinicians. Key requirements for this purpose include (a) sufficiently accurate predictions and (b) model interpretability. Achieving both aspects in parallel is difficult, particularly for datasets with few patients, which are common in the healthcare domain. In such cases, machine learning models encounter mathematically underdetermined systems and may overfit easily on the training data. An important approach to overcome this issue is feature selection, i.e., determining a subset of informative features from the original set of features with respect to the target variable. While potentially raising the predictive performance, feature selection fosters model interpretability by identifying a low number of relevant model parameters to better understand the underlying biological processes that lead to health issues. Interpretability requires that feature selection is stable, i.e., small changes in the dataset do not lead to changes in the selected feature set. A concept to address instability is ensemble feature selection, i.e. the process of repeating the feature selection multiple times on subsets of samples of the original dataset and aggregating results in a meta-model. This thesis presents two approaches for ensemble feature selection, which are tailored towards high-dimensional data in healthcare: the Repeated Elastic Net Technique for feature selection (RENT) and the User-Guided Bayesian Framework for feature selection (UBayFS). While RENT is purely data-driven and builds upon elastic net regularized models, UBayFS is a general framework for ensembles with the capabilities to include expert knowledge in the feature selection process via prior weights and side constraints. A case study modeling the overall survival of cancer patients compares these novel feature selectors and demonstrates their potential in clinical practice. Beyond the selection of single features, UBayFS also allows for selecting whole feature groups (feature blocks) that were acquired from multiple data sources, as those mentioned above. Importance quantification of such feature blocks plays a key role in tracing information about the target variable back to the acquisition modalities. Such information on feature block importance may lead to positive effects on the use of human, technical, and financial resources if systematically integrated into the planning of patient treatment by excluding the acquisition of non-informative features. Since a generalization of feature importance measures to block importance is not trivial, this thesis also investigates and compares approaches for feature block importance rankings. This thesis demonstrates that high-dimensional datasets from multiple data sources in the medical domain can be successfully tackled by the presented approaches for feature selection. Experimental evaluations demonstrate favorable properties of both predictive performance, stability, as well as interpretability of results, which carries a high potential for better data-driven decision support in clinical practice.Moderne datainnsamlingsteknikker i helsevesenet genererer store datamengder fra flere kilder, som for eksempel nye diagnose- og behandlingsmetoder. Noen konkrete eksempler er elektroniske helsejournalsystemer, genomikk og medisinske bilder. Slike pasientkohortdata er ofte ustrukturerte, høydimensjonale og heterogene og hvor klassiske statistiske metoder ikke er tilstrekkelige for optimal utnyttelse av dataene og god informasjonsbasert beslutningstaking. Derfor kan det være lovende å analysere slike datastrukturer ved bruk av moderne maskinlæringsteknikker for å øke forståelsen av pasientenes helseproblemer og for å gi klinikerne en bedre plattform for informasjonsbasert beslutningstaking. Sentrale krav til dette formålet inkluderer (a) tilstrekkelig nøyaktige prediksjoner og (b) modelltolkbarhet. Å oppnå begge aspektene samtidig er vanskelig, spesielt for datasett med få pasienter, noe som er vanlig for data i helsevesenet. I slike tilfeller må maskinlæringsmodeller håndtere matematisk underbestemte systemer og dette kan lett føre til at modellene overtilpasses treningsdataene. Variabelseleksjon er en viktig tilnærming for å håndtere dette ved å identifisere en undergruppe av informative variabler med hensyn til responsvariablen. Samtidig som variabelseleksjonsmetoder kan lede til økt prediktiv ytelse, fremmes modelltolkbarhet ved å identifisere et lavt antall relevante modellparametere. Dette kan gi bedre forståelse av de underliggende biologiske prosessene som fører til helseproblemer. Tolkbarhet krever at variabelseleksjonen er stabil, dvs. at små endringer i datasettet ikke fører til endringer i hvilke variabler som velges. Et konsept for å adressere ustabilitet er ensemblevariableseleksjon, dvs. prosessen med å gjenta variabelseleksjon flere ganger på en delmengde av prøvene i det originale datasett og aggregere resultater i en metamodell. Denne avhandlingen presenterer to tilnærminger for ensemblevariabelseleksjon, som er skreddersydd for høydimensjonale data i helsevesenet: "Repeated Elastic Net Technique for feature selection" (RENT) og "User-Guided Bayesian Framework for feature selection" (UBayFS). Mens RENT er datadrevet og bygger på elastic net-regulariserte modeller, er UBayFS et generelt rammeverk for ensembler som muliggjør inkludering av ekspertkunnskap i variabelseleksjonsprosessen gjennom forhåndsbestemte vekter og sidebegrensninger. En case-studie som modellerer overlevelsen av kreftpasienter sammenligner disse nye variabelseleksjonsmetodene og demonstrerer deres potensiale i klinisk praksis. Utover valg av enkelte variabler gjør UBayFS det også mulig å velge blokker eller grupper av variabler som representerer de ulike datakildene som ble nevnt over. Kvantifisering av viktigheten av variabelgrupper spiller en nøkkelrolle for forståelsen av hvorvidt datakildene er viktige for responsvariablen. Tilgang til slik informasjon kan føre til at bruken av menneskelige, tekniske og økonomiske ressurser kan forbedres dersom informasjonen integreres systematisk i planleggingen av pasientbehandlingen. Slik kan man redusere innsamling av ikke-informative variabler. Siden generaliseringen av viktighet av variabelgrupper ikke er triviell, undersøkes og sammenlignes også tilnærminger for rangering av viktigheten til disse variabelgruppene. Denne avhandlingen viser at høydimensjonale datasett fra flere datakilder fra det medisinske domenet effektivt kan håndteres ved bruk av variabelseleksjonmetodene som er presentert i avhandlingen. Eksperimentene viser at disse kan ha positiv en effekt på både prediktiv ytelse, stabilitet og tolkbarhet av resultatene. Bruken av disse variabelseleksjonsmetodene bærer et stort potensiale for bedre datadrevet beslutningsstøtte i klinisk praksis

    Computational Approaches to Drug Profiling and Drug-Protein Interactions

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    Despite substantial increases in R&D spending within the pharmaceutical industry, denovo drug design has become a time-consuming endeavour. High attrition rates led to a long period of stagnation in drug approvals. Due to the extreme costs associated with introducing a drug to the market, locating and understanding the reasons for clinical failure is key to future productivity. As part of this PhD, three main contributions were made in this respect. First, the web platform, LigNFam enables users to interactively explore similarity relationships between ‘drug like’ molecules and the proteins they bind. Secondly, two deep-learning-based binding site comparison tools were developed, competing with the state-of-the-art over benchmark datasets. The models have the ability to predict offtarget interactions and potential candidates for target-based drug repurposing. Finally, the open-source ScaffoldGraph software was presented for the analysis of hierarchical scaffold relationships and has already been used in multiple projects, including integration into a virtual screening pipeline to increase the tractability of ultra-large screening experiments. Together, and with existing tools, the contributions made will aid in the understanding of drug-protein relationships, particularly in the fields of off-target prediction and drug repurposing, helping to design better drugs faster

    Machine Learning Approaches for Semantic Segmentation on Partly-Annotated Medical Images

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    Semantic segmentation of medical images plays a crucial role in assisting medical practitioners in providing accurate and swift diagnoses; nevertheless, deep neural networks require extensive labelled data to learn and generalise appropriately. This is a major issue in medical imagery because most of the datasets are not fully annotated. Training models with partly-annotated datasets generate plenty of predictions that belong to correct unannotated areas that are categorised as false positives; as a result, standard segmentation metrics and objective functions do not work correctly, affecting the overall performance of the models. In this thesis, the semantic segmentation of partly-annotated medical datasets is extensively and thoroughly studied. The general objective is to improve the segmentation results of medical images via innovative supervised and semi-supervised approaches. The main contributions of this work are the following. Firstly, a new metric, specifically designed for this kind of dataset, can provide a reliable score to partly-annotated datasets with positive expert feedback in their generated predictions by exploiting all the confusion matrix values except the false positives. Secondly, an innovative approach to generating better pseudo-labels when applying co-training with the disagreement selection strategy. This method expands the pixels in disagreement utilising the combined predictions as a guide. Thirdly, original attention mechanisms based on disagreement are designed for two cases: intra-model and inter-model. These attention modules leverage the disagreement between layers (from the same or different model instances) to enhance the overall learning process and generalisation of the models. Lastly, innovative deep supervision methods improve the segmentation results by training neural networks one subnetwork at a time following the order of the supervision branches. The methods are thoroughly evaluated on several histopathological datasets showing significant improvements

    The use of scRNA-seq to characterise the tumour microenvironment of high grade serous ovarian carincoma (HGSOC)

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    High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer. Patients with this disease typically experience relapse in their disease following surgical debulking and initially effective chemotherapy. HGSOC has been intensely studied at the genomic and transcriptomic levels in efforts to advance knowledge of the biological mechanisms that drive the behaviour of this malignancy, and so that new treatment strategies may curb the disease progression relapse. This body of work contributes an optimised protocol for generating robust 10X scRNA-seq libraries from fresh and preserved HGSOC tissue, aiming to dissect the cellular heterogeneity of HGSOC’s Tumour microenvironment (TME). Through unsupervised clustering analysis, it uncovers distinct cellular communities, elucidates transcriptomic signatures across HGSOC tumours, and augments bulk RNA-seq datasets via computational deconvolution, enhancing understanding of HGSOC's cellular complexity across an expanded clinical cohort. The sequencing and analysis of these HGSOC patient tumours revealed 11 distinct cell types, including 2 that are novel in this tumour type; namely ciliated epithelial cells and metallothionein expressing T-cells. These 11 distinct cell types can be broadly categorised into 3 TME components (Tumour, Stroma and Immune) as in other previous tumour scRNA-seq studies. An additional analysis of these components examined the copy number variation (CNV) in the profiled cells and revealed HGSOC tumour cells to be mostly aneuploid while ciliated epithelial cells were diploid. A novel integrative subcluster analysis of HGSOC aneuploid tumour cells identified several apparently tumourigenic gene expression signatures. These include a KRT17+, protease inhibitory signature, an increased cellular metabolism signature, and an immune-reactive signature. Additionally, a ciliated cluster re-emerged within the HGSOC tumour cells, even though the diploid ciliated epithelial cells were not included in the integrative analysis. Finally, the high granularity of HGSOC cellular composition revealed by scRNA-seq is utilised to perform deconvolution analyses to estimate cellular proportions and infer the TME of earlier bulk RNA-seq profiled HGSOC tumour samples. This investigation of earlier sequenced HGSOC samples revealed heterogeneity in the proportions of the TME compartments across the patient cohorts. Survival analysis using these inferred cellular proportions suggest that immune cell presence alone is not associated with survival, but metastatic fibroblast burden in tumour samples is significantly associated with worsen overall survival in HGSOC patients. In conclusion, the laboratory protocol, the scRNA-seq datasets produced, and their analysis and application presented in this work expands the collective knowledge base of HGSOC. Specifically by characterising the cells of the HGSOC tumour microenvironment, and nuances of expression signatures of the malignant cells. The deconvolution approach showcases how scRNA-seq data can expand the clinical utility of earlier RNA-seq HGSOC datasets in a way that is scalable

    Resilient and Scalable Forwarding for Software-Defined Networks with P4-Programmable Switches

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    Traditional networking devices support only fixed features and limited configurability. Network softwarization leverages programmable software and hardware platforms to remove those limitations. In this context the concept of programmable data planes allows directly to program the packet processing pipeline of networking devices and create custom control plane algorithms. This flexibility enables the design of novel networking mechanisms where the status quo struggles to meet high demands of next-generation networks like 5G, Internet of Things, cloud computing, and industry 4.0. P4 is the most popular technology to implement programmable data planes. However, programmable data planes, and in particular, the P4 technology, emerged only recently. Thus, P4 support for some well-established networking concepts is still lacking and several issues remain unsolved due to the different characteristics of programmable data planes in comparison to traditional networking. The research of this thesis focuses on two open issues of programmable data planes. First, it develops resilient and efficient forwarding mechanisms for the P4 data plane as there are no satisfying state of the art best practices yet. Second, it enables BIER in high-performance P4 data planes. BIER is a novel, scalable, and efficient transport mechanism for IP multicast traffic which has only very limited support of high-performance forwarding platforms yet. The main results of this thesis are published as 8 peer-reviewed and one post-publication peer-reviewed publication. The results cover the development of suitable resilience mechanisms for P4 data planes, the development and implementation of resilient BIER forwarding in P4, and the extensive evaluations of all developed and implemented mechanisms. Furthermore, the results contain a comprehensive P4 literature study. Two more peer-reviewed papers contain additional content that is not directly related to the main results. They implement congestion avoidance mechanisms in P4 and develop a scheduling concept to find cost-optimized load schedules based on day-ahead forecasts

    Security and Privacy for Modern Wireless Communication Systems

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    The aim of this reprint focuses on the latest protocol research, software/hardware development and implementation, and system architecture design in addressing emerging security and privacy issues for modern wireless communication networks. Relevant topics include, but are not limited to, the following: deep-learning-based security and privacy design; covert communications; information-theoretical foundations for advanced security and privacy techniques; lightweight cryptography for power constrained networks; physical layer key generation; prototypes and testbeds for security and privacy solutions; encryption and decryption algorithm for low-latency constrained networks; security protocols for modern wireless communication networks; network intrusion detection; physical layer design with security consideration; anonymity in data transmission; vulnerabilities in security and privacy in modern wireless communication networks; challenges of security and privacy in node–edge–cloud computation; security and privacy design for low-power wide-area IoT networks; security and privacy design for vehicle networks; security and privacy design for underwater communications networks

    A machine learning and directed network optimization approach to uncover TP53 regulatory patterns

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    TP53, the Guardian of the Genome, is the most frequently mutated gene in human cancers and the functional characterization of its regulation is fundamental. To address this we employ two strategies: machine learning to predict the mutation status of TP53 from transcriptomic data, and directed regulatory networks to reconstruct the effect of mutations on the transcipt levels of TP53 targets. Using data from established databases (Cancer Cell Line Encyclopedia, The Cancer Genome Atlas), machine learning could predict the mutation status, but not resolve different mutations. On the contrary, directed network optimization allowed to infer the TP53 regulatory profile across: (1) mutations, (2) irradiation in lung cancer, and (3) hypoxia in breast cancer, and we could observe differential regulatory profiles dictated by (1) mutation type, (2) deleterious consequences of the mutation, (3) known hotspots, (4) protein changes, (5) stress condition (irradiation/hypoxia). This is an important first step toward using regulatory networks for the characterization of the functional consequences of mutations, and could be extended to other perturbations, with implications for drug design and precision medicine

    LIPIcs, Volume 261, ICALP 2023, Complete Volume

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    LIPIcs, Volume 261, ICALP 2023, Complete Volum
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