Computational Intelligence for Life Sciences

Computational Intelligence (CI) is a computer science discipline encompassing the theory, design, development and application of biologically and linguistically derived computational paradigms. Traditionally, the main elements of CI are Evolutionary Computation, Swarm Intelligence, Fuzzy Logic, and Neural Networks. CI aims at proposing new algorithms able to solve complex computational problems by taking inspiration from natural phenomena. In an intriguing turn of events, these nature-inspired methods have been widely adopted to investigate a plethora of problems related to nature itself. In this paper we present a variety of CI methods applied to three problems in life sciences, highlighting their effectiveness: we describe how protein folding can be faced by exploiting Genetic Programming, the inference of haplotypes can be tackled using Genetic Algorithms, and the estimation of biochemical kinetic parameters can be performed by means of Swarm Intelligence. We show that CI methods can generate very high quality solutions, providing a sound methodology to solve complex optimization problems in life sciences

Haplotype estimation in polyploids using DNA sequence data

Polyploid organisms possess more than two copies of their core genome and therefore contain k>2 haplotypes for each set of ordered genomic variants. Polyploidy occurs often within the plant kingdom, among others in important corps such as potato (k=4) and wheat (k=6). Current sequencing technologies enable us to read the DNA and detect genomic variants, but cannot distinguish between the copies of the genome, each inherited from one of the parents. To detect inheritance patterns in populations, it is necessary to know the haplotypes, as alleles that are in linkage over the same chromosome tend to be inherited together. In this work, we develop mathematical optimisation algorithms to indirectly estimate haplotypes by looking into overlaps between the sequence reads of an individual, as well as into the expected inheritance of the alleles in a population. These algorithm deal with sequencing errors and random variations in the counts of reads observed from each haplotype. These methods are therefore of high importance for studying the genetics of polyploid crops. </p

Ant Colony Optimization

Ant Colony Optimization (ACO) is the best example of how studies aimed at understanding and modeling the behavior of ants and other social insects can provide inspiration for the development of computational algorithms for the solution of difficult mathematical problems. Introduced by Marco Dorigo in his PhD thesis (1992) and initially applied to the travelling salesman problem, the ACO field has experienced a tremendous growth, standing today as an important nature-inspired stochastic metaheuristic for hard optimization problems. This book presents state-of-the-art ACO methods and is divided into two parts: (I) Techniques, which includes parallel implementations, and (II) Applications, where recent contributions of ACO to diverse fields, such as traffic congestion and control, structural optimization, manufacturing, and genomics are presented

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications

AIRO 2016. 46th Annual Conference of the Italian Operational Research Society. Emerging Advances in Logistics Systems Trieste, September 6-9, 2016 - Abstracts Book

The AIRO 2016 book of abstract collects the contributions from the conference participants. The AIRO 2016 Conference is a special occasion for the Italian Operations Research community, as AIRO annual conferences turn 46th edition in 2016. To reflect this special occasion, the Programme and Organizing Committee, chaired by Walter Ukovich, prepared a high quality Scientific Programme including the first initiative of AIRO Young, the new AIRO poster section that aims to promote the work of students, PhD students, and Postdocs with an interest in Operations Research. The Scientific Programme of the Conference offers a broad spectrum of contributions covering the variety of OR topics and research areas with an emphasis on “Emerging Advances in Logistics Systems”. The event aims at stimulating integration of existing methods and systems, fostering communication amongst different research groups, and laying the foundations for OR integrated research projects in the next decade. Distinct thematic sections follow the AIRO 2016 days starting by initial presentation of the objectives and features of the Conference. In addition three invited internationally known speakers will present Plenary Lectures, by Gianni Di Pillo, Frédéric Semet e Stefan Nickel, gathering AIRO 2016 participants together to offer key presentations on the latest advances and developments in OR’s research

Advanced Immunoinformatics Approaches for Precision Medicine

Genomic sequencing and other ’-omic’ technologies are slowly changing biomedical practice. As a result, patients now can be treated based on their molecular profile. Especially the immune system’s variability, in particular that of the human leukocyte antigen (HLA) gene cluster, makes such a paradigm indispensable when treating illnesses such as cancer, autoimmune diseases, or infectious diseases. It can be, however, costly and time-consuming to determine the HLA genotype with traditional means, as these methods do not utilize often pre-existing sequencing data. We therefore proposed an algorithmic approach that can use these data sources to infer the HLA genotype. HLA genotyping inference can be cast into a set covering problem under special biological constraints and can be solved efficiently via integer linear programming. Our proposed approach outperformed previously published methods and remains one of the most accurate methods to date. We then introduced two applications in which a HLA-based stratification is vital for the efficacy of the treatment and the reduction of its adverse effects. In the first example, we dealt with the optimal design of string-of-beads vaccines (SOB). We developed a mathematical model that maximizes the efficacy of such vaccines while minimizing their side effects based on a given HLA distribution. Comparisons of our optimally designed SOB with experimentally tested designs yielded promising results. In the second example, we considered the problem of anti-drug antibody (ADA) formation of biotherapeutics caused by HLA presented peptides. We combined a new statistical model for mutation effect prediction together with a quantitative measure of immunogenicity to formulate an optimization problem that finds alterations to reduce the risk of ADA formation. To efficiently solve this bi-objective problem, we developed a distributed solver that is up to 25-times faster than state-of-the art solvers. We used our approach to design the C2 domain of factor VIII, which is linked to ADA formation in hemophilia A. Our experimental evaluations of the proposed designs are encouraging and demonstrate the prospects of our approach. Bioinformatics is an integral part of modern biomedical research. The translation of advanced methods into clinical use is often complicated. To ease the translation, we developed a programming library for computational immunology and used it to implement a Galaxy-based web server for vaccine design and a KNIME extension for desktop PCs. These platforms allow researchers to develop their own immunoinformatics workflows utilizing the platform’s graphical programming capabilities

Dissecting the molecular basis of foot-and-mouth disease virus evolution

Foot-and-mouth disease virus (FMDV) causes the most contagious transboundary disease of animals, affecting both wild and domestic cloven-hoofed animals. Similarly to other RNA viruses, FMDV is highly variable as a result of the inherent low fidelity of the viral RNA-dependent RNA polymerase. The accumulation of this variability and relatedness between FMDV sequences was used to provide evidence for modes of transmission (fomite) as well as a constant clock rate across two FMDV topotypes (~8.70 x 10-3 substitutions/site/year), during the 1967 UK FMD epidemic, using full genome consensus sequencing. However, during an epidemic, virus replicates within multiple animals, where it is also replicating and evolving within different tissues and cells. Each scale of evolution, from a single cell to multiple animals across the globe, involves evolutionary processes that shape the viral diversity generated below the level of the consensus. During this PhD project, next-generation sequencing (NGS) was used to dissect the fine scale viral population diversity of FMDV. Collaboration with the Institute of Biodiversity, Animal Health and Comparative Medicine at the University of Glasgow provided the specialist bioinformatic and statistical capabilities required for the analysis of NGS datasets. As part of this collaboration, a new systematic approach was developed to process NGS data and distinguish genuine mutations from artefacts. Additionally, evolutionary models were applied to this data to estimate parameters such as the genome-wide mutation rate of FMDV (upper limit of 7.8 x 10-4 per nt). Analysis of the mutation spectra generated from a clonal control study established a mutation frequency threshold of 0.5% above which there can be confidence that 95% of mutations are real in the sense that they are present in the sampled virus population. This threshold, together with an optimized protocol, was used for the more extensive investigation of within and between host viral population dynamics during transmission. Analysis of mutation spectra and site-specific mutations revealed that intra-host bottlenecks are typically more pronounced than inter-host bottlenecks. NGS analysis has distinguished between the population structure of multiple samples taken from a single host, which may provide the means to reconstruct both intra- and inter-host transmission routes in the future. A more sophisticated understanding of viral diversity at its finest scales could hold the key to the better understanding of viral pathogenesis and, therefore development of effective and sustainable disease treatment and control strategies

Quantum Speed-ups for Boolean Satisfiability and Derivative-Free Optimization

In this thesis, we have considered two important problems, Boolean satisfiability (SAT) and derivative free optimization in the context of large scale quantum computers. In the first part, we survey well known classical techniques for solving satisfiability. We compute the approximate time it would take to solve SAT instances using quantum techniques and compare it with state-of-the heart classical heuristics employed annually in SAT competitions. In the second part of the thesis, we consider a few classically well known algorithms for derivative free optimization which are ubiquitously employed in engineering problems. We propose a quantum speedup to this classical algorithm by using techniques of the quantum minimum finding algorithm. In the third part of the thesis, we consider practical applications in the fields of bio-informatics, petroleum refineries and civil engineering which involve solving either satisfiability or derivative free optimization. We investigate if using known quantum techniques to speedup these algorithms directly translate to the benefit of industries which invest in technology to solve these problems. In the last section, we propose a few open problems which we feel are immediate hurdles, either from an algorithmic or architecture perspective to getting a convincing speedup for the practical problems considered