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MalaCards: A Comprehensive Automatically-Mined Database of Human Diseases

Noa Rappaport, Michal Twik, Noam Nativ, Gil Stelzer, Iris Bahir, Tsippi Iny Stein, Marilyn Safran, Doron Lancet
2014 Current Protocols in Bioinformatics  
Systems medicine provides insights into mechanisms of human diseases, and expedites the development of better diagnostics and drugs. To facilitate such strategies, we initiated MalaCards, a compendium of human diseases and their annotations, integrating and often remodeling information from 64 data sources. MalaCards employs, among others, the proven automatic data-mining strategies established in the construction of GeneCards, our widely used compendium of human genes. The development of
more » ... rds poses many algorithmic challenges, such as disease name unification, integrated classification, gene-disease association, and disease-targeted expression analysis. MalaCards displays a Web card for each of >19,000 human diseases, with 17 sections, including textual summaries, related diseases, related genes, genetic variations and tests, and relevant publications. Also included are a powerful search engine and a variety of categorized disease lists. This unit describes two basic protocols to search and browse MalaCards effectively.
doi:10.1002/0471250953.bi0124s47 pmid:25199789 fatcat:vowmssjxt5c5pnc56rviyj4ot4

MOESM2 of Genome analysis and knowledge-driven variant interpretation with TGex

Dvir Dahary, Yaron Golan, Yaron Mazor, Ofer Zelig, Ruth Barshir, Michal Twik, Tsippi Iny Stein, Guy Rosner, Revital Kariv, Fei Chen, Qiang Zhang, Yiping Shen (+3 others)
2019 Figshare  
Additional file 2. TGex report for the trichohepatoenteric syndrome Demo example
doi:10.6084/m9.figshare.11480619 fatcat:3hgdptj3rbgxldp5sb354ma7m4

MalaCards: an integrated compendium for diseases and their annotation

Noa Rappaport, Noam Nativ, Gil Stelzer, Michal Twik, Yaron Guan-Golan, Tsippi Iny Stein, Iris Bahir, Frida Belinky, C. Paul Morrey, Marilyn Safran, Doron Lancet
2013 Database: The Journal of Biological Databases and Curation  
Citation details: Rappaport,N., Nativ,N., Stelzer,G., et al. MalaCards: an integrated compendium for diseases and their annotation.
doi:10.1093/database/bat018 pmid:23584832 pmcid:PMC3625956 fatcat:ju462m3cezgqtkai2jjrdvatuq

Genome analysis and knowledge-driven variant interpretation with TGex

Dvir Dahary, Yaron Golan, Yaron Mazor, Ofer Zelig, Ruth Barshir, Michal Twik, Tsippi Iny Stein, Guy Rosner, Revital Kariv, Fei Chen, Qiang Zhang, Yiping Shen (+3 others)
2019 BMC Medical Genomics  
The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient's phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform,
more » ... remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex's main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex's broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards' recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters. Examining use-cases from a variety of TGex users world-wide, we demonstrate its high diagnostic yields (42% for single exome and 50% for trios in 1500 rare genetic disease cases) and critical actionable genetic findings. The platform's support for integration with EHR and LIMS through dedicated APIs facilitates automated retrieval of patient data for TGex's customizable reporting engine, establishing a rapid and cost-effective workflow for an entire range of clinical genetic testing, including rare disorders, cancer predisposition, tumor biopsies and health screening. TGex is an innovative tool for the annotation, analysis and prioritization of coding and non-coding genomic variants. It provides access to an extensive knowledgebase of genomic annotations, with intuitive and flexible configuration options, allows quick adaptation, and addresses various workflow requirements. It thus simplifies and accelerates variant interpretation in clinical genetics workflows, with remarkable diagnostic yield, as exemplified in the described use cases. TGex is available at http://tgex.genecards.org/.
doi:10.1186/s12920-019-0647-8 pmid:31888639 pmcid:PMC6937949 fatcat:ixi7j3mqqzflrgzaj5wwwb3xjm

Rational confederation of genes and diseases: NGS interpretation via GeneCards, MalaCards and VarElect

Noa Rappaport, Simon Fishilevich, Ron Nudel, Michal Twik, Frida Belinky, Inbar Plaschkes, Tsippi Iny Stein, Dana Cohen, Danit Oz-Levi, Marilyn Safran, Doron Lancet
2017 BioMedical Engineering OnLine  
A key challenge in the realm of human disease research is next generation sequencing (NGS) interpretation, whereby identified filtered variant-harboring genes are associated with a patient's disease phenotypes. This necessitates bioinformatics tools linked to comprehensive knowledgebases. The GeneCards suite databases, which include GeneCards (human genes), MalaCards (human diseases) and PathCards (human pathways) together with additional tools, are presented with the focus on MalaCards utility
more » ... for NGS interpretation as well as for large scale bioinformatic analyses.
doi:10.1186/s12938-017-0359-2 pmid:28830434 pmcid:PMC5568599 fatcat:nr5iblpqh5bn5glqnrgelrdehm

MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search

Noa Rappaport, Michal Twik, Inbar Plaschkes, Ron Nudel, Tsippi Iny Stein, Jacob Levitt, Moran Gershoni, C. Paul Morrey, Marilyn Safran, Doron Lancet
2016 Nucleic Acids Research  
The MalaCards human disease database (http://www. malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across
more » ... -conflicting sources, providing effective annotation consolidation. A central feature is a balanced Genes section, with scores reflecting the strength of disease-gene associations. This is accompanied by other gene-related disease information such as pathways, mouse phenotypes and GO-terms, stemming from MalaCards' affiliation with the GeneCards Suite of databases. MalaCards' capacity to inter-link information from complementary sources, along with its elaborate search function, relational database infrastructure and convenient data dumps, allows it to tackle its rich disease annotation landscape, and facilitates systems analyses and genome sequence interpretation. MalaCards adopts a 'flat' disease-card approach, but each card is mapped to popular hierarchical ontologies (e.g. International Classification of Diseases, Human Phenotype Ontology and Unified Medical Language System) and also contains information about multi-level relations among diseases, thereby providing an optimal tool for disease representation and scrutiny.
doi:10.1093/nar/gkw1012 pmid:27899610 pmcid:PMC5210521 fatcat:gc65doqdurcxrdfs4fbqhanxbi

GeneHancer: genome-wide integration of enhancers and target genes in GeneCards

Simon Fishilevich, Ron Nudel, Noa Rappaport, Rotem Hadar, Inbar Plaschkes, Tsippi Iny Stein, Naomi Rosen, Asher Kohn, Michal Twik, Marilyn Safran, Doron Lancet, Dana Cohen
2017 Database: The Journal of Biological Databases and Curation  
These authors contributed equally to this work. Citation details: Fishilevich,S., Nudel,R., Rappaport,N. et al. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards. Abstract A major challenge in understanding gene regulation is the unequivocal identification of enhancer elements and uncovering their connections to genes. We present GeneHancer, a novel database of human enhancers and their inferred target genes, in the framework of GeneCards. First, we integrated a
more » ... l of 434 000 reported enhancers from four different genome-wide databases: the Encyclopedia of DNA Elements (ENCODE), the Ensembl regulatory build, the functional annotation of the mammalian genome (FANTOM) project and the VISTA Enhancer Browser. Employing an integration algorithm that aims to remove redundancy, GeneHancer portrays 285 000 integrated candidate enhancers (covering 12.4% of the genome), 94 000 of which are derived from more than one source, and each assigned an annotation-derived confidence score. GeneHancer subsequently links enhancers to genes, using: tissue co-expression correlation between genes and enhancer RNAs, as well as enhancer-targeted transcription factor genes; expression quantitative trait loci for variants within enhancers; and capture Hi-C, a promoter-specific genome conformation assay. The individual scores based on each of these four methods, along with gene-enhancer genomic distances, form the basis for GeneHancer's combinatorial likelihood-based scores for enhancer-gene pairing. Finally, we define 'elite' enhancergene relations reflecting both a high-likelihood enhancer definition and a strong enhancer-gene association. GeneHancer predictions are fully integrated in the widely used GeneCards Suite, whereby candidate enhancers and their annotations are displayed on every relevant GeneCard. This assists in the mapping of non-coding variants to enhancers, and via the linked genes, forms a basis for variant-phenotype interpretation of whole-genome sequences in health and disease.
doi:10.1093/database/bax028 pmid:28605766 pmcid:PMC5467550 fatcat:xslg453wargdbalhgq7rmj73pq

ORDB, HORDE, ODORactor and other on-line knowledge resources of olfactory receptor-odorant interactions

Luis Marenco, Rixin Wang, Robert McDougal, Tsviya Olender, Michal Twik, Elspeth Bruford, Xinyi Liu, Jian Zhang, Doron Lancet, Gordon Shepherd, Chiquito Crasto
2016 Database: The Journal of Biological Databases and Curation  
Citation details: Marenco,L., Wang,R., McDougal,R. et al. ORDB, HORDE, ODORactor and other on-line knowledge resources of olfactory receptor-odorant interactions. Abstract We present here an exploration of the evolution of three well-established, web-based resources dedicated to the dissemination of information related to olfactory receptors (ORs) and their functional ligands, odorants. These resources are: the Olfactory Receptor Database (ORDB), the Human Olfactory Data Explorer (HORDE) and
more » ... Ractor. ORDB is a repository of genomic and proteomic information related to ORs and other chemosensory receptors, such as taste and pheromone receptors. Three companion databases closely integrated with ORDB are OdorDB, ORModelDB and OdorMapDB; these resources are part of the SenseLab suite of databases (http://senselab.med.yale.edu). HORDE (http://genome.weizmann.ac.il/horde/) is a semi-automatically populated database of the OR repertoires of human and several mammals. ODORactor (http://mdl.shsmu.edu.cn/ ODORactor/) provides information related to OR-odorant interactions from the perspective of the odorant. All three resources are connected to each other via web-links.
doi:10.1093/database/baw132 pmid:27694208 pmcid:PMC5045865 fatcat:es3j5ulb4resbhbyg6z4b5s7qi

VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Gil Stelzer, Inbar Plaschkes, Danit Oz-Levi, Anna Alkelai, Tsviya Olender, Shahar Zimmerman, Michal Twik, Frida Belinky, Simon Fishilevich, Ron Nudel, Yaron Guan-Golan, David Warshawsky (+9 others)
2016 BMC Genomics  
Next generation sequencing (NGS) provides a key technology for deciphering the genetic underpinnings of human diseases. Typical NGS analyses of a patient depict tens of thousands non-reference coding variants, but only one or very few are expected to be significant for the relevant disorder. In a filtering stage, one employs family segregation, rarity in the population, predicted protein impact and evolutionary conservation as a means for shortening the variation list. However, narrowing down
more » ... rther towards culprit disease genes usually entails laborious seeking of gene-phenotype relationships, consulting numerous separate databases. Thus, a major challenge is to transition from the few hundred shortlisted genes to the most viable disease-causing candidates.
doi:10.1186/s12864-016-2722-2 pmid:27357693 pmcid:PMC4928145 fatcat:zbmio3et65h23phhmmgyve46z4

Distinct Expression/Function of Potassium and Chloride Channels Contributes to the Diverse Volume Regulation in Cortical Astrocytes of GFAP/EGFP Mice

Jana Benesova, Vendula Rusnakova, Pavel Honsa, Helena Pivonkova, David Dzamba, Mikael Kubista, Miroslava Anderova, Michal Hetman
2012 PLoS ONE  
The PCR data revealed the existence of two astrocytic subpopulations markedly differing in their gene expression levels for inwardly rectifying K + channels (Kir4.1), K 2P channels (TREK-1 and TWIK-1)  ...  Barium chloride (1 mM), which was shown to block the inwardly rectifying K + channel TWIK-1 [27] , markedly reduced the swelling of HR-astrocytes, thus suggesting that TWIK-1 channels contribute to K  ...  On the other hand, HR-astrocytes strongly express TWIK-1, which is responsible for enhanced K + uptake and their swelling.  ... 
doi:10.1371/journal.pone.0029725 pmid:22253765 pmcid:PMC3256164 fatcat:prfoqkft6ffo7dvf6mm7wrcm2q

Potassium Channel in the Mitochondria of Human Keratinocytes

Renata Toczyłowska-Mamińska, Anna Olszewska, Michał Laskowski, Piotr Bednarczyk, Krzysztof Skowronek, Adam Szewczyk
2014 Journal of Investigative Dermatology  
Immunofluorescent methods and western blotting have suggested the possibility of the presence of TASK-1, 2 and 3 (tandem pore domain acidsensitive K þ channels), TREK-1 (TWIK-related K þ channel) and 2  ...  , and TRAAK (TWIK-related arachidonic acid-stimulated K þ channel) channels in plasma membrane of these cells and the TASK-3 channel in the mitochondria of keratinocytes (Kang et al., 2007; Rusznak et  ... 
doi:10.1038/jid.2013.422 pmid:24126847 fatcat:7jddvyj5bve5rle2ijndqxi3me

Molecular factors in migraine

Marta Kowalska, Michał Prendecki, Wojciech Kozubski, Margarita Lianeri, Jolanta Dorszewska
2016 OncoTarget  
the insertion/deletion polymorphism Abbreviations: MA -migraine with aura; MO -migraine without aura; MTHFR -methylenetetrahydrofolate reductase; KCNK18 -potassium channel subfamily K member 18; TRESK -TWIK-related  ... 
doi:10.18632/oncotarget.9367 pmid:27191890 pmcid:PMC5226615 fatcat:sku63h6sv5c2xkosuyn4je756e

Mitochondrialne kanały potasowe: podsumowanie

Adam Szewczyk, Piotr Bednarczyk, Justyna Jędraszko, Rafał Paweł Kampa, Piotr Koprowski, Milena Krajewska, Shur Kucman, Bogusz Kulawiak, Michał Laskowski, Daria Rotko, Aleksandra Sęk, Agnieszka Walewska (+2 others)
2018 Postepy biochemii  
Up to now, only one member of this family, TWIK-Related Acid-Sensitive K + Channel 3 (TASK-3), has been shown to reside in mitochondria [15] [16] [17] [18] [19] .  ...  dependent potassium channels; mitoSK Ca -mitochondrial small--conductance K Ca channel; OMM -outer mitochondrial membrane, PAX -paxilline; ROMK2 -renal outer medullary K + channel (Kir1.1b); TASK-3 -TWIK-related  ... 
doi:10.18388/pb.2018_132 fatcat:urqjl2u4srhf5pcowl4x3zqq3i

Altered Astrocytic Swelling in the Cortex of α-Syntrophin-Negative GFAP/EGFP Mice

Miroslava Anderova, Jana Benesova, Michaela Mikesova, David Dzamba, Pavel Honsa, Jan Kriska, Olena Butenko, Vendula Novosadova, Lukas Valihrach, Mikael Kubista, Lesia Dmytrenko, Michal Cicanic (+2 others)
2014 PLoS ONE  
channels ClC1 and ClC2; Glul encodes glutamine synthetase (GS); Trpv4 encodes transient receptor potential vanilloid 4 channels TRPV4; Kcnk1, Kcnk2, Kcnk9 and Kcnk10 code two pore domain K + channels TWIK  ...  channels ClC1 and ClC2; Glul encodes glutamine synthetase; Trpv4 encodes the transient receptor potential vanilloid 4 channel TRPV4; Kcnk1, Kcnk2, Kcnk9 and Kcnk10 code the two pore domain K + channels TWIK  ... 
doi:10.1371/journal.pone.0113444 pmid:25426721 pmcid:PMC4245134 fatcat:t44yogtjjzebbgdm63fd6tiskm
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