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Article ; Online: VDJviz: a versatile browser for immunogenomics data.

Bagaev, Dmitriy V / Zvyagin, Ivan V / Putintseva, Ekaterina V / Izraelson, Mark / Britanova, Olga V / Chudakov, Dmitriy M / Shugay, Mikhail

BMC genomics

2016 Volume 17, Page(s) 453

Abstract: ... key repertoire characteristics such as spectratype, repertoire clonality, V-(D)-J recombination ...

Abstract	Background: The repertoire of T- and B-cell receptor sequences encodes the antigen specificity of adaptive immunity system, determines its present state and guides its ability to mount effective response against encountered antigens in future. High throughput sequencing of immune repertoires (Rep-Seq) is a promising technique that allows to profile millions of antigen receptors of an individual in a single experiment. While a substantial number of tools for mapping and assembling Rep-Seq data were published recently, the field still lacks an intuitive and flexible tool that can be used by researchers with little or no computational background for in-depth analysis of immune repertoire profiles. Results: Here we report VDJviz, a web tool that can be used to browse, analyze and perform quality control of Rep-Seq results generated by various pre-processing software. On a set of real data examples we show that VDJviz can be used to explore key repertoire characteristics such as spectratype, repertoire clonality, V-(D)-J recombination patterns and to identify shared clonotypes. We also demonstrate the utility of VDJviz in detection of critical Rep-Seq biases such as artificial repertoire diversity and cross-sample contamination. Conclusions: VDJviz is a versatile and lightweight tool that can be easily employed by biologists, immunologists and immunogeneticists for routine analysis and quality control of Rep-Seq data. The software is freely available for non-commercial purposes, and can be downloaded from: https://github.com/antigenomics/vdjviz .
MeSH term(s)	B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Clonal Evolution/genetics ; Cluster Analysis ; Complementarity Determining Regions/genetics ; Computational Biology/methods ; Computational Biology/standards ; Genomics/methods ; Genomics/standards ; Humans ; Software ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; V(D)J Recombination ; Web Browser
Chemical Substances	Complementarity Determining Regions
Language	English
Publishing date	2016-06-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-016-2799-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: MAGERI: Computational pipeline for molecular-barcoded targeted resequencing.

Shugay, Mikhail / Zaretsky, Andrew R / Shagin, Dmitriy A / Shagina, Irina A / Volchenkov, Ivan A / Shelenkov, Andrew A / Lebedin, Mikhail Y / Bagaev, Dmitriy V / Lukyanov, Sergey / Chudakov, Dmitriy M

PLoS computational biology

2017 Volume 13, Issue 5, Page(s) e1005480

Abstract: Unique molecular identifiers (UMIs) show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in ... ...

Abstract	Unique molecular identifiers (UMIs) show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in multiple areas, including cancer diagnostics, thus demanding dedicated software and algorithms. Here we introduce MAGERI, a computational pipeline that efficiently handles all caveats of UMI-based analysis to obtain high-fidelity mutation profiles and call ultra-rare variants. Using an extensive set of benchmark datasets including gold-standard biological samples with known variant frequencies, cell-free DNA from tumor patient blood samples and publicly available UMI-encoded datasets we demonstrate that our method is both robust and efficient in calling rare variants. The versatility of our software is supported by accurate results obtained for both tumor DNA and viral RNA samples in datasets prepared using three different UMI-based protocols.
MeSH term(s)	Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Computational Biology/methods ; Databases, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neoplasms/genetics ; RNA, Viral/genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/methods ; Software
Chemical Substances	Biomarkers, Tumor ; RNA, Viral
Language	English
Publishing date	2017-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1005480
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: MAGERI

Mikhail Shugay / Andrew R Zaretsky / Dmitriy A Shagin / Irina A Shagina / Ivan A Volchenkov / Andrew A Shelenkov / Mikhail Y Lebedin / Dmitriy V Bagaev / Sergey Lukyanov / Dmitriy M Chudakov

PLoS Computational Biology, Vol 13, Iss 5, p e

Computational pipeline for molecular-barcoded targeted resequencing.

2017 Volume 1005480

Abstract	Unique molecular identifiers (UMIs) show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in multiple areas, including cancer diagnostics, thus demanding dedicated software and algorithms. Here we introduce MAGERI, a computational pipeline that efficiently handles all caveats of UMI-based analysis to obtain high-fidelity mutation profiles and call ultra-rare variants. Using an extensive set of benchmark datasets including gold-standard biological samples with known variant frequencies, cell-free DNA from tumor patient blood samples and publicly available UMI-encoded datasets we demonstrate that our method is both robust and efficient in calling rare variants. The versatility of our software is supported by accurate results obtained for both tumor DNA and viral RNA samples in datasets prepared using three different UMI-based protocols.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires.

Shugay, Mikhail / Bagaev, Dmitriy V / Turchaninova, Maria A / Bolotin, Dmitriy A / Britanova, Olga V / Putintseva, Ekaterina V / Pogorelyy, Mikhail V / Nazarov, Vadim I / Zvyagin, Ivan V / Kirgizova, Vitalina I / Kirgizov, Kirill I / Skorobogatova, Elena V / Chudakov, Dmitriy M

PLoS computational biology

2015 Volume 11, Issue 11, Page(s) e1004503

Abstract: Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell ... ...

Abstract	Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools.
MeSH term(s)	Adolescent ; Adult ; Child ; Cluster Analysis ; Computational Biology/methods ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Sclerosis/genetics ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Sequence Analysis, DNA/methods ; Software ; Twins/genetics ; Young Adult
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2015-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1004503
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Article ; Online: VDJtools

Mikhail Shugay / Dmitriy V Bagaev / Maria A Turchaninova / Dmitriy A Bolotin / Olga V Britanova / Ekaterina V Putintseva / Mikhail V Pogorelyy / Vadim I Nazarov / Ivan V Zvyagin / Vitalina I Kirgizova / Kirill I Kirgizov / Elena V Skorobogatova / Dmitriy M Chudakov

PLoS Computational Biology, Vol 11, Iss 11, p e

Unifying Post-analysis of T Cell Receptor Repertoires.

2015 Volume 1004503

Abstract	Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2015-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium.

Bagaev, Dmitry V / Vroomans, Renske M A / Samir, Jerome / Stervbo, Ulrik / Rius, Cristina / Dolton, Garry / Greenshields-Watson, Alexander / Attaf, Meriem / Egorov, Evgeny S / Zvyagin, Ivan V / Babel, Nina / Cole, David K / Godkin, Andrew J / Sewell, Andrew K / Kesmir, Can / Chudakov, Dmitriy M / Luciani, Fabio / Shugay, Mikhail

Nucleic acids research

2019 Volume 48, Issue D1, Page(s) D1057–D1062

Abstract: Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes ... ...

Abstract	Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes that facilitate database querying and real-world data analysis. The increased yield of TCR specificity identification methods and the overall increase in the number of studies in the field has allowed us to expand the database more than 5-fold. Furthermore, several new analysis methods are included. For example, batch annotation of TCR repertoire sequencing samples allows for annotating large datasets on-line. Using recently developed bioinformatic methods for TCR motif mining, we have built a reduced set of high-quality TCR motifs that can be used for both training TCR specificity predictors and matching against TCRs of interest. These additions enhance the versatility of the VDJdb in the task of exploring T-cell antigen specificities. The database is available at https://vdjdb.cdr3.net.
MeSH term(s)	Amino Acid Sequence ; Computational Biology/methods ; Databases, Genetic ; High-Throughput Nucleotide Sequencing ; Humans ; Nucleotide Motifs ; Position-Specific Scoring Matrices ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/genetics ; Sequence Analysis, DNA ; Software ; V(D)J Recombination ; Web Browser
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2019-10-03
Publishing country	England
Document type	Journal Article ; 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/gkz874
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: VDJdb: a curated database of T-cell receptor sequences with known antigen specificity.

Shugay, Mikhail / Bagaev, Dmitriy V / Zvyagin, Ivan V / Vroomans, Renske M / Crawford, Jeremy Chase / Dolton, Garry / Komech, Ekaterina A / Sycheva, Anastasiya L / Koneva, Anna E / Egorov, Evgeniy S / Eliseev, Alexey V / Van Dyk, Ewald / Dash, Pradyot / Attaf, Meriem / Rius, Cristina / Ladell, Kristin / McLaren, James E / Matthews, Katherine K / Clemens, E Bridie /

Douek, Daniel C / Luciani, Fabio / van Baarle, Debbie / Kedzierska, Katherine / Kesmir, Can / Thomas, Paul G / Price, David A / Sewell, Andrew K / Chudakov, Dmitriy M

Nucleic acids research

2017 Volume 46, Issue D1, Page(s) D419–D427

Abstract: The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. ... ...

Abstract	The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antigens/chemistry ; Antigens/immunology ; Antigens/metabolism ; Binding Sites ; Databases, Protein ; High-Throughput Nucleotide Sequencing ; Humans ; Internet ; Macaca mulatta ; Major Histocompatibility Complex/genetics ; Major Histocompatibility Complex/immunology ; Mice ; Models, Molecular ; Molecular Sequence Annotation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Single-Cell Analysis ; Software ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
Chemical Substances	Antigens ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2017-10-05
Publishing country	England
Document type	Journal Article ; 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/gkx760
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: External Multicenter Study of Reliability and Reproducibility for Lower Cervical Spine Injuries Classification Systems-Part 1: A Comparison of Morphological Schemes.

Grin, Andrey / Krylov, Vladimir / Lvov, Ivan / Talypov, Aleksandr / Dzukaev, Dmitriy / Kordonskiy, Anton / Smirnov, Vladimir / Karanadze, Vasily / Abdukhalikov, Boburmirzo / Khushnazarov, Ulugbek / Aleynikova, Irina / Kazakova, Elza / Bogdanova, Olesya / Peyker, Alexander / Semchenko, Vitaliy / Aksenov, Andrey / Borzenkov, Anton / Gulyy, Vladimir / Torchinov, Soslan /

Bagaev, Sergey / Toporskiy, Anton / Nikitin, Andrey / Arakelyan, Sevak / Martikyan, Avetik / Oshchepkov, Stanislav / Hovrin, Dmitriy / Kojev, Aslan / Khalatyan, Musheg

Global spine journal

2019 Volume 10, Issue 6, Page(s) 682–691

Abstract: Study design: Multicenter observational survey study.: Objectives: To quantify and compare the inter- and intraobserver reliability of Allen-Fergusson (A-F), Harris, Argenson, and AOSpine (AOS) classifications for cervical spine injuries, in a ... ...

Abstract	Study design: Multicenter observational survey study. Objectives: To quantify and compare the inter- and intraobserver reliability of Allen-Fergusson (A-F), Harris, Argenson, and AOSpine (AOS) classifications for cervical spine injuries, in a multicentric survey of neurosurgeons with different levels of experience. Methods: We used data of 64 consecutive patients. Totally, 37 surgeons (from 7 centers), were included in the study. The initial assessment was returned by 36 raters. The second assessment performed after 1.5 months included 24 raters. Results: We received 15 111 answers for 3840 evaluations. Raters reached a fair general agreement of the A-F scale, while the experienced group achieved κ = 0.39. While all groups showed moderate interrater reliability for primary assessment of Harris scale (κ = 0.44), the κ value for experts decreased from 0.58 to 0.49. The Argenson scale demonstrated moderate and substantial agreement among all raters (κ = 0.47 and κ = 0.55, respectively). The AOS scheme primary assessment general kappa value for all types of injuries and across all raters was 0.49, reaching substantial agreement among experts (κ = 0.62) with moderate agreement across beginner and intermediate groups (κ = 0.48 and κ = 0.44, respectively). The second assessment general agreement kappa value reached 0.56. Conclusions: We found the highest values of interobserver agreement and reproducibility among surgeons with different levels of experience with Argenson and AOSpine classifications. The AOSpine scale additionally incorporated more detailed description of compression injuries and facet-joint fractures. Agreement levels reached for Allen-Fergusson and Harris scales were fair and moderate, respectively, indicating difficulty of their application in clinical practice, especially by junior specialists.
Language	English
Publishing date	2019-08-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2648287-3
ISSN	2192-5690 ; 2192-5682
ISSN (online)	2192-5690
ISSN	2192-5682
DOI	10.1177/2192568219868218
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: External Multicenter Study of Reliability and Reproducibility for Lower Cervical Spine Injuries Classification Systems-Part 2: An Analysis of the Subaxial Cervical Spine Injury Classification and Cervical Spine Injury Severity Score Scale.

Grin, Andrey / Krylov, Vladimir / Lvov, Ivan / Talypov, Aleksandr / Dzukaev, Dmitriy / Kordonskiy, Anton / Smirnov, Vladimir / Karanadze, Vasily / Abdukhalikov, Boburmirzo / Khushnazarov, Ulugbek / Airapetyan, Artem / Dmitriev, Aleksandr / Kaykov, Aleksandr / Peyker, Alexander / Semchenko, Vitaliy / Aksenov, Andrey / Borzenkov, Anton / Gulyy, Vladimir / Torchinov, Soslan /

Bagaev, Sergey / Toporskiy, Anton / Kalandari, Alik / Kasatkin, Denis / Sytnik, Aleksey / Lebedev, Valeriy / Epifanov, Dmitry / Hovrin, Dmitriy / Feniksov, Victor / Choriev, Daniyar

Global spine journal

2019 Volume 11, Issue 1, Page(s) 99–107

Abstract: Study design: A multicenter observational survey.: Objective: To quantify and compare inter- and intraobserver reliability of the subaxial cervical spine injury classification (SLIC) and the cervical spine injury severity score (CSISS) in a ... ...

Abstract	Study design: A multicenter observational survey. Objective: To quantify and compare inter- and intraobserver reliability of the subaxial cervical spine injury classification (SLIC) and the cervical spine injury severity score (CSISS) in a multicentric survey of neurosurgeons with different experience levels. Methods: Data concerning 64 consecutive patients who had undergone cervical spine surgery between 2013 and 2017 was evaluated, and we surveyed 37 neurosurgeons from 7 different clinics. All raters were divided into 3 groups depending on their level of experience. Two assessment procedures were performed. Results: For the SLIC, we observed excellent agreement regarding management among experienced surgeons, whereas agreement among less experienced neurosurgeons was moderate and almost twice as unlikely. The sensitivity of SLIC relating to treatment tactics reached as high as 92.2%. For the CSISS, agreement regarding management ranged from medium to substantial, depending on a neurosurgeon's experience. For less experienced neurosurgeons, the level of agreement concerning surgical management was the same as for the SLIC in not exceeding a moderate level. However, this scale had insufficient sensitivity (slightly exceeding 50%). The reproducibility of both scales was excellent among all raters regardless of their experience level. Conclusions: Our study demonstrated better management reliability, sensitivity, and reproducibility for the SLIC, which provided moderate interrater agreement with moderate to excellent intraclass correlation coefficient indicators for all raters. The CSISS demonstrated high reproducibility; however, large variability in answers prevented raters from reaching a moderate level of agreement. Magnetic resonance imaging integration may increase sensitivity of CSISS in relation to fracture management.
Language	English
Publishing date	2019-12-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2648287-3
ISSN	2192-5690 ; 2192-5682
ISSN (online)	2192-5690
ISSN	2192-5682
DOI	10.1177/2192568219896546
Database	MEDical Literature Analysis and Retrieval System OnLINE

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