Ivan Sović

Fast and sensitive mapping of nanopore sequencing reads with GraphMap.

Realizing the democratic promise of nanopore sequencing requires the development of new bioinformatics approaches to deal with its specific error characteristics. Here we present GraphMap, a mapping algorithm designed to analyse nanopore sequencing reads, which progressively refines candidate alignments to robustly handle potentially high-error rates and a fast graph traversal to align long reads with speed and high precision (>95%). Evaluation on MinION sequencing data sets against short- and long-read mappers indicates that GraphMap increases mapping sensitivity by 10–80% and maps >95% of bases. GraphMap alignments enabled single-nucleotide variant calling on the human genome with increased sensitivity (15%) over the next best mapper, precise detection of structural variants from length 100 bp to 4 kbp, and species and strain-specific identification of pathogens using MinION reads. GraphMap is available open source under the MIT license at https://github.com/isovic/graphmap.

Fast and accurate de novo genome assembly from long uncorrected reads

The assembly of long reads from Pacific Biosciences and Oxford Nanopore Technologies typically requires resource-intensive error-correction and consensus-generation steps to obtain high-quality assemblies. We show that the error-correction step can be omitted and that high-quality consensus sequences can be generated efficiently with a SIMD-accelerated, partial-order alignment-based, stand-alone consensus module called Racon. Based on tests with PacBio and Oxford Nanopore data sets, we show that Racon coupled with miniasm enables consensus genomes with similar or better quality than state-of-the-art methods while being an order of magnitude faster.

Scalable Distributed Computing Hierarchy: Cloud, Fog and Dew Computing

The paper considers the conceptual approach for organization of the vertical hierarchical links between the scalable distributed computing paradigms: Cloud Computing, Fog Computing and Dew Computing. In this paper, the Dew Computing is described and recognized as a new structural layer in the existing distributed computing hierarchy. In the existing computing hierarchy, the Dew computing is positioned as the ground level for the Cloud and Fog computing paradigms. Vertical, complementary, hierarchical division from Cloud to Dew Computing satisfies the needs of high- and low-end computing demands in everyday life and work. These new computing paradigms lower the cost and improve the performance, particularly for concepts and applications such as the Internet of Things (IoT) and the Internet of Everything (IoE). In addition, the Dew computing paradigm will require new programming models that will efficiently reduce the complexity and improve the productivity and usability of scalable distributed computing, following the principles of High-Productivity computing.

Evaluation of hybrid and non-hybrid methods for de novo assembly of nanopore reads

MOTIVATION Recent emergence of nanopore sequencing technology set a challenge for established assembly methods. In this work, we assessed how existing hybrid and non-hybrid de novo assembly methods perform on long and error prone nanopore reads. RESULTS We benchmarked five non-hybrid (in terms of both error correction and scaffolding) assembly pipelines as well as two hybrid assemblers which use third generation sequencing data to scaffold Illumina assemblies. Tests were performed on several publicly available MinION and Illumina datasets of Escherichia coli K-12, using several sequencing coverages of nanopore data (20×, 30×, 40× and 50×). We attempted to assess the assembly quality at each of these coverages, in order to estimate the requirements for closed bacterial genome assembly. For the purpose of the benchmark, an extensible genome assembly benchmarking framework was developed. Results show that hybrid methods are highly dependent on the quality of NGS data, but much less on the quality and coverage of nanopore data and perform relatively well on lower nanopore coverages. All non-hybrid methods correctly assemble the E. coli genome when coverage is above 40×, even the non-hybrid method tailored for Pacific Biosciences reads. While it requires higher coverage compared to a method designed particularly for nanopore reads, its running time is significantly lower. AVAILABILITY AND IMPLEMENTATION https://github.com/kkrizanovic/NanoMark CONTACT mile.sikic@fer.hr SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Fast and sensitive mapping of error-prone nanopore sequencing reads with GraphMap

Exploiting the power of nanopore sequencing requires the development of new bioinformatics approaches to deal with its specific error characteristics. We present the first nanopore read mapper (GraphMap) that uses a read-funneling paradigm to robustly handle variable error rates and fast graph traversal to align long reads with speed and very high precision (>95%). Evaluation on MinION sequencing datasets against short and long-read mappers indicates that GraphMap increases mapping sensitivity by at least 15-80%. GraphMap alignments are the first to demonstrate consensus calling with <1 error in 100,000 bases, variant calling on the human genome with 76% improvement in sensitivity over the next best mapper (BWA-MEM), precise detection of structural variants from 100bp to 4kbp in length and species and strain-specific identification of pathogens using MinION reads. GraphMap is available open source under the MIT license at https://github.com/isovic/graphmap.

The Sum-Connectivity Index - An Additive Variant of the Randić Connectivity Index

This review discusses structure-property modeling applications of a novel variant of the Randic connectivity index that is called the sum-connectivity index. We compare published one-descriptor quantitative structure-property relationship (QSPR) models obtained with the new sum-connectivity index and with the Randic connectivity index, called here the product-connectivity index. Additionally, the efficiency of both variants of connectivity indices in QSPR modeling is tested on five datasets of alkanes and two datasets of polycyclic hydrocarbons. Several physicochemical properties of alkanes (i.e. boiling and melting points, retention index, molar volume, molar refraction, heat of vaporization, standard Gibbs energy of formation, critical temperature, critical pressure, surface tension, density) and π- electronic energies of two sets of polycyclic hydrocarbons were correlated with the product- and sum-connectivity indices. A comparison of these QSPR models shows that both variants of connectivity indices are equivalent, and only slightly (but not significantly) better results are obtained with the sum-connectivity index. Inter-correlations between the product- and sum-connectivity indices are mostly linear with a slope very close to 1.0 for alkanes, and with a slope more different from 1.0 (0.88) for polycyclic compounds. The comparative analysis presented here supports the use of the sumconnectivity index in QSPR/QSAR studies together with the product-connectivity index. Further studies on larger and more heterogeneous datasets should test the sum-connectivity index in QSPR/QSAR models.

Implementation of Advanced Historical Computer Architectures

Present day development of FPGAs enables us to implement even very complex computer architectures of the past with very few resources. Furthermore, they enable prospective electronic engineers, computer designers and computer scientists to experiment with those architectures, to gain experience and primarily to open up new possible perspectives on future computer architecture designs. In this chapter we present an implementation of the Cray-1 computer system on the E2LP platform. The initial publicly available generic FPGA design of the Cray processor was modified to fit the specifications of the E2LP board and the Spartan-6 FPGA. Aside from customizing the original design, a translator for the Cray Assembly Language was developed, as well as a basic bootloader to provide the use of this implementation as a teaching tool. The Cray-1 implementation facilitates a perfect learning setup for students of all levels. It can guide a student from the very basic stages which involve the synthesis and transfer of the Cray-1 design onto the E2LP board up to the embedded software design in a real, comprehensive, and historically industrially very significant Cray Assembly Language. Additionally, many advanced laboratory exercises can be made with the core Cray processor implementation on the E2LP board. The expansion of the Cray-1 design into a Cray-XMP, Cray-2 or some other computer from that series enables deep insight in the correspondence of instruction sets, registers and interdependent timings.

RNA Transcriptome Mapping with GraphMap

Next generation sequencing technologies have made RNA sequencing widely accessible and applicable in many areas of research. In recent years, 3rd generation sequencing technologies have matured and are slowly replacing NGS for DNA sequencing. This paper presents a novel tool for RNA mapping guided by gene annotations. The tool is an adapted version of a previously developed DNA mapper – GraphMap, tailored for third generation sequencing data, such as those produced by Pacific Biosciences or Oxford Nanopore Technologies devices. It uses gene annotations to generate a transcriptome, uses a DNA mapping algorithm to map reads to the transcriptome, and finally transforms the mappings back to genome coordinates. Modified version of GraphMap is compared on several synthetic datasets to the state-of-the-art RNAseq mappers enabled to work with third generation sequencing data. The results show that our tool outperforms other tools in general mapping quality.

Exercises for Embedded Engineering Learning Platform

In this chapter we present basic set of laboratory exercises, developed under the Embedded Computer Engineering Learning Platform (E2LP) project, with illustrative laboratory examples covering the embedded engineering learning objectives. In order to satisfy the widest range of learning methods and models and to be successful in supporting different types of students, library of laboratory exercises contains a detailed manual/catalog documentation that for each exercise explains the problem covering by the exercise, provide an overview of the required background theoretical knowledge and lead the student to a solution without revealing the actual steps and decisions he or she must make. The E2LP library has more than 60 open source laboratory exercises ready to be presented to other universities. The exercises could also be used over the e-learning portal. Additionally, the E2LP platform integrates an augmented reality interface for visualizing, simulating and monitoring invisible principles, phenomena and facts in the field of electronics hardware and education details. Interactive graphical user interface for web catalogue, provides easy navigation through content of the library of laboratory exercises and enables platform users to ask for help, give feedback, and in general discuss projects based on the E2LP board.

Advances in Mathematical Chemistry and Applications Volume 1 (Revised Edition)

Volume 1 includes chapters on mathematical structural descriptors of molecules and biomolecules, applications of partially ordered sets (posets) in chemistry, optimal characterization of molecular complexity using graph theory, different connectivity matrices and their polynomials, use of 2D fingerprints in similaritybased virtual screening, mathematical approaches to molecular structure generation, comparability graphs, applications of molecular topology in drug design, density functional theory of chemical reactivity, application of mathematical descriptors in the quantification of drug-likeness, utility of pharmacophores in drug design, and much more.