LIVIVO - Search results -

Search results

Result 1 - 10 of total 24

Search options

Article ; Online: In Silico Functional Annotation of Genomic Variation.

Butkiewicz, Mariusz / Bush, William S

2016 Volume 88, Page(s) 6.15.1–6.15.17

Abstract: This unit describes the concepts and practical techniques for annotating genomic variants in the human genome to estimate their functional significance. With the rapid increase of available whole exome and whole genome sequencing information for human ... ...

Abstract	This unit describes the concepts and practical techniques for annotating genomic variants in the human genome to estimate their functional significance. With the rapid increase of available whole exome and whole genome sequencing information for human studies, annotation techniques have become progressively more important for highlighting and prioritizing nucleotide variants and their potential impact on genes and other genetic constructs. Here, we present an overview of different types of variant annotation approaches and elaborate on their foundations, assumptions, and the downstream consequences of their use. Computational approaches and tools to assign annotations and to identify variants are reviewed. Further, the general philosophy of assigning potential function to a genetic change within the biological context of a disease is discussed.
MeSH term(s)	Computational Biology/methods ; Computer Simulation ; Genetic Predisposition to Disease/genetics ; Genetic Variation ; Genome, Human/genetics ; Genome-Wide Association Study/methods ; Genomics/methods ; Humans ; Molecular Sequence Annotation/methods ; Reproducibility of Results
Language	English
Publishing date	2016-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2179054-1
ISSN	1934-8258 ; 1934-8266
ISSN (online)	1934-8258
ISSN	1934-8266
DOI	10.1002/0471142905.hg0615s88
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- Full text online
- Order with fees

Article ; Online: Introducing COCOS: codon consequence scanner for annotating reading frame changes induced by stop-lost and frame shift variants.

Butkiewicz, Mariusz / Haines, Jonathan L / Bush, William S

Bioinformatics (Oxford, England)

2017 Volume 33, Issue 10, Page(s) 1561–1562

Abstract: Summary: Reading frame altering genomic variants can impact gene expression levels and the structure of protein products, thus potentially inducing disease phenotypes. Current annotation approaches report the impact of such variants in the context of ... ...

Abstract	Summary: Reading frame altering genomic variants can impact gene expression levels and the structure of protein products, thus potentially inducing disease phenotypes. Current annotation approaches report the impact of such variants in the context of altered DNA sequence only; attributes of the resulting transcript, reading frame and translated protein product are not reported. To remedy this shortcoming, we present a new genetic annotation approach termed Codon Consequence Scanner (COCOS). Implemented as an Ensembl variant effect predictor (VEP) plugin, COCOS captures amino acid sequence alterations stemming from variants that produce an altered reading frame, such as stop-lost variants and small insertions and deletions (InDels). To highlight its significance, COCOS was applied to data from the 1000 Genomes Project. Transcripts affected by stop-lost variants introduce a median of 15 amino acids, while InDels have a more extensive impact with a median of 66 amino acids being incorporated. Captured sequence alterations are written out in FASTA format and can be further analyzed for impact on the underlying protein structure. Availability and implementation: COCOS is available to all users on github: https://github.com/butkiem/COCOS. Contact: mariusz.butkiewicz@case.edu.
MeSH term(s)	Codon ; Frameshift Mutation ; Genomics/methods ; Humans ; INDEL Mutation ; Reading Frames ; Sequence Analysis, DNA/methods ; Sequence Analysis, Protein/methods ; Software
Chemical Substances	Codon
Language	English
Publishing date	2017-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btw820
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2374: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Introducing COCOS: codon consequence scanner for annotating reading frame changes induced by stop-lost and frame shift variants

Butkiewicz, Mariusz / Haines, Jonathan L / Bush, William S

Bioinformatics. 2017 May 15, v. 33, no. 10

2017

Abstract	Summary: Reading frame altering genomic variants can impact gene expression levels and the structure of protein products, thus potentially inducing disease phenotypes. Current annotation approaches report the impact of such variants in the context of altered DNA sequence only; attributes of the resulting transcript, reading frame and translated protein product are not reported. To remedy this shortcoming, we present a new genetic annotation approach termed Codon Consequence Scanner (COCOS). Implemented as an Ensembl variant effect predictor (VEP) plugin, COCOS captures amino acid sequence alterations stemming from variants that produce an altered reading frame, such as stop-lost variants and small insertions and deletions (InDels). To highlight its significance, COCOS was applied to data from the 1000 Genomes Project. Transcripts affected by stop-lost variants introduce a median of 15 amino acids, while InDels have a more extensive impact with a median of 66 amino acids being incorporated. Captured sequence alterations are written out in FASTA format and can be further analyzed for impact on the underlying protein structure. Availability and Implementation: COCOS is available to all users on github: https://github.com/butkiem/COCOS Contact: mariusz.butkiewicz@case.edu
Keywords	DNA ; amino acid sequences ; amino acids ; bioinformatics ; gene expression ; genome ; genomics ; messenger RNA ; nucleotide sequences ; phenotype ; protein products ; scanners ; translation (genetics)
Language	English
Dates of publication	2017-0515
Size	p. 1561-1562.
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/btw820
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Article: Introduction to the BioChemical Library (BCL): An Application-Based Open-Source Toolkit for Integrated Cheminformatics and Machine Learning in Computer-Aided Drug Discovery.

Brown, Benjamin P / Vu, Oanh / Geanes, Alexander R / Kothiwale, Sandeepkumar / Butkiewicz, Mariusz / Lowe, Edward W / Mueller, Ralf / Pape, Richard / Mendenhall, Jeffrey / Meiler, Jens

Frontiers in pharmacology

2022 Volume 13, Page(s) 833099

Abstract: The BioChemical Library (BCL) cheminformatics toolkit is an application-based academic open-source software package designed to integrate traditional small molecule cheminformatics tools with machine learning-based quantitative structure-activity/ ... ...

Abstract	The BioChemical Library (BCL) cheminformatics toolkit is an application-based academic open-source software package designed to integrate traditional small molecule cheminformatics tools with machine learning-based quantitative structure-activity/property relationship (QSAR/QSPR) modeling. In this pedagogical article we provide a detailed introduction to core BCL cheminformatics functionality, showing how traditional tasks (e.g., computing chemical properties, estimating druglikeness) can be readily combined with machine learning. In addition, we have included multiple examples covering areas of advanced use, such as reaction-based library design. We anticipate that this manuscript will be a valuable resource for researchers in computer-aided drug discovery looking to integrate modular cheminformatics and machine learning tools into their pipelines.
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.833099
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: DRUG-DRUG INTERACTION PROFILES OF MEDICATION REGIMENS EXTRACTED FROM A DE-IDENTIFIED ELECTRONIC MEDICAL RECORDS SYSTEM.

Butkiewicz, Mariusz / Restrepo, Nicole A / Haines, Jonathan L / Crawford, Dana C

AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science

2016 Volume 2016, Page(s) 33–40

Abstract: With age, the number of prescribed medications increases and subsequently raises the risk for adverse drug-drug interactions. These adverse effects lower quality of life and increase health care costs. Quantifying the potential burden of adverse effects ... ...

Abstract	With age, the number of prescribed medications increases and subsequently raises the risk for adverse drug-drug interactions. These adverse effects lower quality of life and increase health care costs. Quantifying the potential burden of adverse effects before prescribing medications can be a valuable contribution to health care. This study evaluated medication lists extracted from a subset of the Vanderbilt de-identified electronic medical record system. Reported drugs were cross-referenced with the Kyoto Encyclopedia of Genes and Genomes DRUG database to identify known drug-drug interactions. On average, a medication regimen contained 6.58 medications and 2.68 drug-drug interactions. Here, we quantify the burden of potential adverse events from drug-drug interactions through drug-drug interaction profiles and include a number of alternative medications as provided by the Anatomical Therapeutic Chemical Classification System.
Language	English
Publishing date	2016-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2676378-3
ISSN	2153-4063
ISSN	2153-4063
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: High-Throughput Screening Assay Datasets from the PubChem Database.

Butkiewicz, Mariusz / Wang, Yanli / Bryant, Stephen H / Lowe, Edward W / Weaver, David C / Meiler, Jens

Chemical informatics (Wilmington, Del.)

2017 Volume 3, Issue 1

Abstract: Availability of high-throughput screening (HTS) data in the public domain offers great potential to foster development of ligand-based computer-aided drug discovery (LB-CADD) methods crucial for drug discovery efforts in academia and industry. LB-CADD ... ...

Abstract	Availability of high-throughput screening (HTS) data in the public domain offers great potential to foster development of ligand-based computer-aided drug discovery (LB-CADD) methods crucial for drug discovery efforts in academia and industry. LB-CADD method development depends on high-quality HTS assay data, i.e., datasets that contain both active and inactive compounds. These active compounds are hits from primary screens that have been tested in concentration-response experiments and where the target-specificity of the hits has been validated through suitable secondary screening experiments. Publicly available HTS repositories such as PubChem often provide such data in a convoluted way: compounds that are classified as inactive need to be extracted from the primary screening record. However, compounds classified as active in the primary screening record are not suitable as a set of active compounds for LB-CADD experiments due to high false-positive rate. A suitable set of actives can be derived by carefully analysing results in often up to five or more assays that are used to confirm and classify the activity of compounds. These assays, in part, build on each other. However, often not all hit compounds from the previous screen have been tested. Sometimes a compound can be classified as 'active', though its meaning is 'inactive' on the target of interest as it is 'active' on a different target protein. Here, a curation process of hierarchically related confirmatory screens is illustrated based on two specifically chosen protein use-cases. The subsequent re-upload procedure into PubChem is described for the findings of those two scenarios. Further, we provide nine publicly accessible high quality datasets for future LB-CADD method development that provide a common baseline for comparison of future methods to the scientific community. We also provide a protocol researchers can follow to upload additional datasets for benchmarking.
Language	English
Publishing date	2017-04-26
Publishing country	United States
Document type	Journal Article
ISSN	2470-6973
ISSN (online)	2470-6973
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records.

Restrepo, Nicole A / Butkiewicz, Mariusz / McGrath, Josephine A / Crawford, Dana C

Frontiers in genetics

2016 Volume 7, Page(s) 185

Abstract: Autoimmune diseases represent a significant medical burden affecting up to 5-8% of the U.S.: Population: While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, ... ...

Abstract	Autoimmune diseases represent a significant medical burden affecting up to 5-8% of the U.S. Population: While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, and a single disease approach. Here we performed a targeted genetic association study for cases of multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease (CD) to assess which common genetic variants contribute individually and pleiotropically to disease risk. Joint modeling and pathway analysis combining the three phenotypes were performed to identify common underlying mechanisms of risk of autoimmune conditions. European American cases of MS, RA, and CD, (
Language	English
Publishing date	2016-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2016.00185
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: BCL::EMAS--enantioselective molecular asymmetry descriptor for 3D-QSAR.

Sliwoski, Gregory / Lowe, Edward W / Butkiewicz, Mariusz / Meiler, Jens

Molecules (Basel, Switzerland)

2012 Volume 17, Issue 8, Page(s) 9971–9989

Abstract: Stereochemistry is an important determinant of a molecule's biological activity. Stereoisomers can have different degrees of efficacy or even opposing effects when interacting with a target protein. Stereochemistry is a molecular property difficult to ... ...

Abstract	Stereochemistry is an important determinant of a molecule's biological activity. Stereoisomers can have different degrees of efficacy or even opposing effects when interacting with a target protein. Stereochemistry is a molecular property difficult to represent in 2D-QSAR as it is an inherently three-dimensional phenomenon. A major drawback of most proposed descriptors for 3D-QSAR that encode stereochemistry is that they require a heuristic for defining all stereocenters and rank-ordering its substituents. Here we propose a novel 3D-QSAR descriptor termed Enantioselective Molecular ASymmetry (EMAS) that is capable of distinguishing between enantiomers in the absence of such heuristics. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. A radial-distribution function (RDF) determines a signed volume of tetrahedrons of all triplets of atoms and the molecule center. The descriptor can be enriched with atom-centric properties such as partial charge. This descriptor showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r² = 0.89, q² = 0.78). Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS) for inhibitors and substrates of cytochrome P450 (PUBCHEM AID891).
MeSH term(s)	Algorithms ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Software ; Stereoisomerism
Language	English
Publishing date	2012-08-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules17089971
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.MO 81: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Identification of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Acting at Site Distinct from 2-Methyl-6-(phenylethynyl)-pyridine Binding.

Butkiewicz, Mariusz / Rodriguez, Alice L / Rainey, Shane E / Wieting, Joshua / Luscombe, Vincent B / Stauffer, Shaun R / Lindsley, Craig W / Conn, P Jeffrey / Meiler, Jens

ACS chemical neuroscience

2019 Volume 10, Issue 8, Page(s) 3427–3436

Abstract: As part of the G-protein coupled receptor (GPCR) family, metabotropic glutamate (mGlu) receptors play an important role as drug targets of cognitive diseases. Selective allosteric modulators of mGlu subtype 5 ( ... ...

Abstract	As part of the G-protein coupled receptor (GPCR) family, metabotropic glutamate (mGlu) receptors play an important role as drug targets of cognitive diseases. Selective allosteric modulators of mGlu subtype 5 (mGlu
MeSH term(s)	Allosteric Regulation/drug effects ; Allosteric Site/drug effects ; Animals ; Drug Discovery/methods ; High-Throughput Screening Assays ; Humans ; Receptor, Metabotropic Glutamate 5/chemistry ; Receptor, Metabotropic Glutamate 5/drug effects ; Receptor, Metabotropic Glutamate 5/metabolism ; Structure-Activity Relationship
Chemical Substances	Receptor, Metabotropic Glutamate 5
Language	English
Publishing date	2019-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.8b00227
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Pathway analysis by randomization incorporating structure-PARIS: an update.

Butkiewicz, Mariusz / Cooke Bailey, Jessica N / Frase, Alex / Dudek, Scott / Yaspan, Brian L / Ritchie, Marylyn D / Pendergrass, Sarah A / Haines, Jonathan L

Bioinformatics (Oxford, England)

2016 Volume 32, Issue 15, Page(s) 2361–2363

Abstract: Motivation: We present an update to the pathway enrichment analysis tool 'Pathway Analysis by Randomization Incorporating Structure (PARIS)' that determines aggregated association signals generated from genome-wide association study results. Pathway- ... ...

Abstract	Motivation: We present an update to the pathway enrichment analysis tool 'Pathway Analysis by Randomization Incorporating Structure (PARIS)' that determines aggregated association signals generated from genome-wide association study results. Pathway-based analyses highlight biological pathways associated with phenotypes. PARIS uses a unique permutation strategy to evaluate the genomic structure of interrogated pathways, through permutation testing of genomic features, thus eliminating many of the over-testing concerns arising with other pathway analysis approaches. Results: We have updated PARIS to incorporate expanded pathway definitions through the incorporation of new expert knowledge from multiple database sources, through customized user provided pathways, and other improvements in user flexibility and functionality. Availability and implementation: PARIS is freely available to all users at https://ritchielab.psu.edu/software/paris-download Contact: jnc43@case.edu Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Databases, Factual ; Genome-Wide Association Study ; Genomics ; Humans ; Software
Language	English
Publishing date	2016-08-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btw130
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2374: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito