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  1. Article ; Online: Ribose-Map: a bioinformatics toolkit to map ribonucleotides embedded in genomic DNA.

    Gombolay, Alli L / Vannberg, Fredrik O / Storici, Francesca

    Nucleic acids research

    2018  Volume 47, Issue 1, Page(s) e5

    Abstract: Recent advances in high-throughput sequencing techniques have made it possible to tag ribonucleoside monophosphates (rNMPs) embedded in genomic DNA for sequencing. rNMP sequencing experiments generate large, complex datasets that require efficient, ... ...

    Abstract Recent advances in high-throughput sequencing techniques have made it possible to tag ribonucleoside monophosphates (rNMPs) embedded in genomic DNA for sequencing. rNMP sequencing experiments generate large, complex datasets that require efficient, scalable software that can accurately map embedded rNMPs independently of the particular sequencing technique used. Current computational pipelines designed to map rNMPs embedded in genomic DNA are customized for data generated using only one type of rNMP sequencing technique. To standardize the processing and analysis of rNMP sequencing experiments, we developed Ribose-Map. Through a series of analytical modules, Ribose-Map transforms raw sequencing data into summary datasets and publication-ready visualizations of results, allowing biologists to identify sites of embedded rNMPs, study the nucleotide sequence context of these rNMPs and explore their genome-wide distribution. By accommodating data from any of the available rNMP sequencing techniques, Ribose-Map can increase the reproducibility of rNMP sequencing experiments and enable a head-to-head comparison of these experiments.
    MeSH term(s) Base Sequence/genetics ; Computational Biology/methods ; DNA/genetics ; Genome, Fungal/genetics ; Genomics ; Humans ; Ribonucleotides/genetics ; Ribose/genetics ; Saccharomyces cerevisiae/genetics ; Software
    Chemical Substances Ribonucleotides ; Ribose (681HV46001) ; DNA (9007-49-2)
    Language English
    Publishing date 2018-06-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gky874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Using earth mover's distance for viral outbreak investigations.

    Melnyk, Andrew / Knyazev, Sergey / Vannberg, Fredrik / Bunimovich, Leonid / Skums, Pavel / Zelikovsky, Alex

    BMC genomics

    2020  Volume 21, Issue Suppl 5, Page(s) 582

    Abstract: Background: RNA viruses mutate at extremely high rates, forming an intra-host viral population of closely related variants, which allows them to evade the host's immune system and makes them particularly dangerous. Viral outbreaks pose a significant ... ...

    Abstract Background: RNA viruses mutate at extremely high rates, forming an intra-host viral population of closely related variants, which allows them to evade the host's immune system and makes them particularly dangerous. Viral outbreaks pose a significant threat for public health, and, in order to deal with it, it is critical to infer transmission clusters, i.e., decide whether two viral samples belong to the same outbreak. Next-generation sequencing (NGS) can significantly help in tackling outbreak-related problems. While NGS data is first obtained as short reads, existing methods rely on assembled sequences. This requires reconstruction of the entire viral population, which is complicated, error-prone and time-consuming.
    Results: The experimental validation using sequencing data from HCV outbreaks shows that the proposed algorithm can successfully identify genetic relatedness between viral populations, infer transmission direction, transmission clusters and outbreak sources, as well as decide whether the source is present in the sequenced outbreak sample and identify it.
    Conclusions: Introduced algorithm allows to cluster genetically related samples, infer transmission directions and predict sources of outbreaks. Validation on experimental data demonstrated that algorithm is able to reconstruct various transmission characteristics. Advantage of the method is the ability to bypass cumbersome read assembly, thus eliminating the chance to introduce new errors, and saving processing time by allowing to use raw NGS reads.
    MeSH term(s) Algorithms ; Disease Outbreaks ; Hepacivirus/genetics ; High-Throughput Nucleotide Sequencing ; RNA Viruses
    Language English
    Publishing date 2020-12-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-020-06982-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: KAnalyze: a fast versatile pipelined k-mer toolkit.

    Audano, Peter / Vannberg, Fredrik

    Bioinformatics (Oxford, England)

    2014  Volume 30, Issue 14, Page(s) 2070–2072

    Abstract: Motivation: Converting nucleotide sequences into short overlapping fragments of uniform length, k-mers, is a common step in many bioinformatics applications. While existing software packages count k-mers, few are optimized for speed, offer an ... ...

    Abstract Motivation: Converting nucleotide sequences into short overlapping fragments of uniform length, k-mers, is a common step in many bioinformatics applications. While existing software packages count k-mers, few are optimized for speed, offer an application programming interface (API), a graphical interface or contain features that make it extensible and maintainable. We designed KAnalyze to compete with the fastest k-mer counters, to produce reliable output and to support future development efforts through well-architected, documented and testable code. Currently, KAnalyze can output k-mer counts in a sorted tab-delimited file or stream k-mers as they are read. KAnalyze can process large datasets with 2 GB of memory. This project is implemented in Java 7, and the command line interface (CLI) is designed to integrate into pipelines written in any language.
    Results: As a k-mer counter, KAnalyze outperforms Jellyfish, DSK and a pipeline built on Perl and Linux utilities. Through extensive unit and system testing, we have verified that KAnalyze produces the correct k-mer counts over multiple datasets and k-mer sizes.
    Availability and implementation: KAnalyze is available on SourceForge: https://sourceforge.net/projects/kanalyze/.
    MeSH term(s) Algorithms ; Chromosomes, Human, Pair 1/chemistry ; Humans ; Sequence Analysis, DNA/methods ; Software
    Language English
    Publishing date 2014-03-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btu152
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mapping-free variant calling using haplotype reconstruction from k-mer frequencies.

    Audano, Peter A / Ravishankar, Shashidhar / Vannberg, Fredrik O

    Bioinformatics (Oxford, England)

    2017  Volume 34, Issue 10, Page(s) 1659–1665

    Abstract: Motivation: The standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or ... ...

    Abstract Motivation: The standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or is too distant from known references. De novo assembly or hybrid methods can recover genomic variation, but the cost of computation is often much higher. We developed a novel k-mer algorithm and software implementation, Kestrel, capable of characterizing densely packed SNPs and large indels without mapping, assembly or de Bruijn graphs.
    Results: When applied to mosaic penicillin binding protein (PBP) genes in Streptococcus pneumoniae, we found near perfect concordance with assembled contigs at a fraction of the CPU time. Multilocus sequence typing (MLST) with this approach was able to bypass de novo assemblies. Kestrel has a very low false-positive rate when applied to the whole genome, and while Kestrel identified many variants missed by other methods, limitations of a purely k-mer based approach affect overall sensitivity.
    Availability and implementation: Source code and documentation for a Java implementation of Kestrel can be found at https://github.com/paudano/kestrel. All test code for this publication is located at https://github.com/paudano/kescases.
    Contact: paudano@gatech.edu or fredrik.vannberg@biology.gatech.edu.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Algorithms ; Genome, Bacterial ; Genomics/methods ; Haplotypes ; Multilocus Sequence Typing/methods ; Polymorphism, Genetic ; Software ; Streptococcus pneumoniae/genetics
    Language English
    Publishing date 2017-11-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btx753
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: New

    Gallo, Juan E / Torres, Isaura / Gómez, Oscar M / Rishishwar, Lavanya / Vannberg, Fredrik / Jordan, I King / McEwen, Juan G / Clay, Oliver K

    Journal of fungi (Basel, Switzerland)

    2021  Volume 7, Issue 7

    Abstract: Histoplasmosis is a systemic fungal disease caused by the ... ...

    Abstract Histoplasmosis is a systemic fungal disease caused by the pathogen
    Language English
    Publishing date 2021-07-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2784229-0
    ISSN 2309-608X ; 2309-608X
    ISSN (online) 2309-608X
    ISSN 2309-608X
    DOI 10.3390/jof7070544
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

    Srinivasan, Swetha / Vannberg, Fredrik O / Dixon, J Brandon

    Scientific reports

    2016  Volume 6, Page(s) 24436

    Abstract: It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, ... ...

    Abstract It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.
    MeSH term(s) Animals ; B-Lymphocytes/physiology ; Endothelial Cells/physiology ; Exosomes/physiology ; Lymph Nodes/cytology ; Lymph Nodes/physiology ; Lymphatic System/cytology ; Lymphatic System/physiology ; Lymphatic Vessels/physiology ; Macrophages/physiology ; Male ; Mice ; Mice, Inbred BALB C
    Language English
    Publishing date 2016-04-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep24436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mapping-free variant calling using haplotype reconstruction from k-mer frequencies

    Audano, Peter A / Ravishankar, Shashidhar / Vannberg, Fredrik O / Berger, Bonnie

    Bioinformatics. 2018 May 15, v. 34, no. 10

    2018  

    Abstract: The standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or is too ... ...

    Abstract The standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or is too distant from known references. De novo assembly or hybrid methods can recover genomic variation, but the cost of computation is often much higher. We developed a novel k-mer algorithm and software implementation, Kestrel, capable of characterizing densely packed SNPs and large indels without mapping, assembly or de Bruijn graphs. When applied to mosaic penicillin binding protein (PBP) genes in Streptococcus pneumoniae, we found near perfect concordance with assembled contigs at a fraction of the CPU time. Multilocus sequence typing (MLST) with this approach was able to bypass de novo assemblies. Kestrel has a very low false-positive rate when applied to the whole genome, and while Kestrel identified many variants missed by other methods, limitations of a purely k-mer based approach affect overall sensitivity. Source code and documentation for a Java implementation of Kestrel can be found at https://github.com/paudano/kestrel. All test code for this publication is located at https://github.com/paudano/kescases. Supplementary data are available at Bioinformatics online.
    Keywords DNA ; Streptococcus pneumoniae ; algorithms ; binding proteins ; bioinformatics ; computer software ; enzymes ; genes ; genetic variation ; graphs ; haplotypes ; loci ; multilocus sequence typing ; penicillins ; single nucleotide polymorphism
    Language English
    Dates of publication 2018-0515
    Size p. 1659-1665.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 1468345-3
    ISSN 1460-2059 ; 1367-4811 ; 1367-4803
    ISSN (online) 1460-2059 ; 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btx753
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

    Huang, Cai / Mezencev, Roman / McDonald, John F / Vannberg, Fredrik

    PloS one

    2017  Volume 12, Issue 10, Page(s) e0186906

    Abstract: Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of ... ...

    Abstract Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.
    MeSH term(s) Algorithms ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Gene Expression ; Humans ; Machine Learning ; Neoplasms/drug therapy ; Neoplasms/genetics ; Precision Medicine
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2017-10-26
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0186906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The first complete genome of the simian malaria parasite Plasmodium brasilianum.

    Bajic, Marko / Ravishankar, Shashidhar / Sheth, Mili / Rowe, Lori A / Pacheco, M Andreina / Patel, Dhruviben S / Batra, Dhwani / Loparev, Vladimir / Olsen, Christian / Escalante, Ananias A / Vannberg, Fredrik / Udhayakumar, Venkatachalam / Barnwell, John W / Talundzic, Eldin

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 19802

    Abstract: Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by ... ...

    Abstract Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has been available. Previously, we reported a draft genome for P. brasilianum, and here we report the completed genome for P. brasilianum. The genome is 31.4 Mb in size and comprises 14 chromosomes, the mitochondrial genome, the apicoplast genome, and 29 unplaced contigs. The chromosomes consist of 98.4% nucleotide sites that are identical to the P. malariae genome, the closest evolutionarily related species hypothesized to be the same species as P. brasilianum, with 41,125 non-synonymous SNPs (0.0722% of genome) identified between the two genomes. Furthermore, P. brasilianum had 4864 (82.1%) genes that share 80% or higher sequence similarity with 4970 (75.5%) P. malariae genes. This was demonstrated by the nearly identical genomic organization and multiple sequence alignments for the merozoite surface proteins msp3 and msp7. We observed a distinction in the repeat lengths of the circumsporozoite protein (CSP) gene sequences between P. brasilianum and P. malariae. Our results demonstrate a 97.3% pairwise identity between the P. brasilianum and the P. malariae genomes. These findings highlight the phylogenetic proximity of these two species, suggesting that P. malariae and P. brasilianum are strains of the same species, but this could not be fully evaluated with only a single genomic sequence for each species.
    MeSH term(s) Animals ; Humans ; Parasites/genetics ; Phylogeny ; Plasmodium/genetics ; Malaria/parasitology ; Sequence Analysis, DNA
    Language English
    Publishing date 2022-11-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-20706-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution.

    Lie, Lively / Biliya, Shweta / Vannberg, Fredrik / Wartell, Roger M

    Journal of molecular evolution

    2016  Volume 82, Issue 2-3, Page(s) 81–92

    Abstract: The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support ... ...

    Abstract The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support condensation of activated nucleotides into RNA oligomers, RNA ligation by the hairpin ribozyme, and RNA synthesis by a RNA polymerase ribozyme. In the current study, we examined the activity of a hammerhead ribozyme (HHR) in frozen solution. The Schistosoma mansoni hammerhead ribozyme, which predominantly cleaves RNA, can ligate its cleaved products (P1 and P2) with yields up to ~23 % in single turnover experiments at 25 °C in the presence of Mg(2+). Our studies show that this HHR ligates RNA oligomers in frozen solution in the absence of divalent cations. Citrate and other anions that exhibit strong ion-water affinity enhanced ligation. Yields up to 43 % were observed in one freeze-thaw cycle and a maximum of 60 % was obtained after several freeze-thaw cycles using wild-type P1 and P2. Truncated and mutated P1 substrates were ligated to P2 with yields of 14-24 % in one freeze-thaw cycle. A pool of P2 substrates with mixtures of all four bases at five positions were ligated with P1 in frozen solution. High-throughput sequencing indicated that 70 of the 1024 possible P2 sequences were represented in ligated products at 1000 or more read counts per million reads. The results indicate that the HHR can ligate a range of short RNA oligomers into an ensemble of diverse sequences in ice.
    MeSH term(s) Animals ; Aptamers, Nucleotide/biosynthesis ; Base Sequence ; Catalysis ; Cryopreservation ; DNA-Directed RNA Polymerases/genetics ; Freezing ; Hydrogen-Ion Concentration ; Kinetics ; Ligation ; Nucleic Acid Conformation ; RNA ; RNA, Catalytic/metabolism ; Schistosoma mansoni/metabolism
    Chemical Substances Aptamers, Nucleotide ; RNA, Catalytic ; hairpin ribozyme ; hammerhead ribozyme ; RNA (63231-63-0) ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
    Language English
    Publishing date 2016-03
    Publishing country Germany
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 120148-7
    ISSN 1432-1432 ; 0022-2844
    ISSN (online) 1432-1432
    ISSN 0022-2844
    DOI 10.1007/s00239-016-9729-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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