The GeneCards Suite

Safran, Marilyn; Rosen, Naomi; Twik, Michal; Barshir, Ruth; Stein, Tsippi Iny; Dahary, Dvir; Fishilevich, Simon; Lancet, Doron

doi:10.1007/978-981-16-5812-9_2

Cited by 350 publications

(377 citation statements)

References 81 publications

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“…In contrast, the strongest signals in AFR, AMR, and EUR were seen in OR51B6 , which corresponds to rs5006884 with known association to fetal hemoglobin (HbF) levels in sickle cell anemia, a classical example of balancing selection driven disease 28 . This SNP lies upstream of the β-globin locus control region and is in close proximity to several candidate enhancers of HBG2 29 , which codes for the gamma-2 subunit of HbF. ClinVar SNPs 30 were also investigated, showing possible selection in CYP2D6 and OPRM1 related to drug responses, and in IRF5 and HAO , associated with systemic lupus erythematosus and calcium oxalate urolithiasis respectively (see Methods and Supplemental Table 5).…”

Section: Resultsmentioning

confidence: 99%

Improved detection of evolutionary selection highlights potential bias from different sequencing strategies in complex genomic-regions

et al. 2021

Preprint

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Balancing selection occurs when different evolutionary pressures impact the fitness of multiple alleles, resulting in increased allelic diversity in the population. A new statistical method was developed to test for selection, improving inference by using efficient Bayesian techniques to test for density and strength of linkage disequilibrium. Evolutionary simulation studies showed that the method consistently outperformed existing methods. Using this methodology, we tested for novel signals of balancing selection genome wide in 500 samples from phased trios. Several novel signals of selection appeared in CYP2A7, GPC6, and CNR2 across multiple ancestries. Additionally, tests in SIRPA demonstrate dramatically strong selection signal, significantly higher than previously observed. Well-known signals around olfactory genes and the MHC, containing HLA genes associated with the immune response, also demonstrated strong signatures of selection. So, utilizing data from the 17th IHIW, a follow up analysis was then performed by leveraging over seven thousand HLA typed samples by NGS; in contrast, the genome wide scan did not include a detailed characterization of the HLA genes. The strongest signals observed in the IHIW samples were in DQA1 and DQB1 in or around exon 2, the portion of the gene responsible for antigen presentation and most likely to be under environmental and evolutionary pressure. Our new statistical approach and analysis suggest novel evolutionary pressure in new regions and additionally highlight the importance of improved sequencing and characterization of variation across the extended MHC and other critical regions.

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Section: Resultsmentioning

confidence: 99%

Improved detection of evolutionary selection highlights potential bias from different sequencing strategies in complex genomic-regions

et al. 2021

Preprint

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“…The targets related to mechanisms of action of RP were obtained from the following databases: GeneCards ( https://www.genecards.org/ ) [ 9 ], OMIM ( https://omim.org ) [ 10 ], TTD (therapeutic Target Database, bidd.nus.edu.sg) [ 11 ], DrugBank ( https://www.drugbank.ca/ ) [ 12 ], and the Herb database ( https://herb.ac.cn/ ) [ 13 ]. Targets identification was done using the key words; “radiation pneumonitistis”, “radiation pneumonia”, “acute radiation pneumonitis”, “radiation induced pneumonia”, “radioactive pneumonitis” and “radiation-induced pneumonitis”.…”

Section: Methodsmentioning

confidence: 99%

Rules of Chinese Herbal Intervention of Radiation Pneumonia Based on Network Pharmacology and Data Mining

Dan

Xue

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the mechanism and principles of traditional Chinese medicine (TCM) in the management of radiation pneumonia. Methods. The targets of radiation pneumonia were obtained by screening the GeneCards, OMIM, TTD, DrugBank, and HERB databases, analyzing ADME parameters. In addition, compounds and Chinese herbs that can act on the targets were screened from the TCMSP database. The core target compounds for TCM were used to construct the target-compound, compound-traditional Chinese medicine, and target-compound-traditional Chinese medicine networks. These networks were further used to select the core targets, compounds, and TCM. The binding strength between the core targets and compounds was determined using AutoDock Vina. The trajectory for the molecular dynamics simulation was completed by Desmond version 2020. Results. A total of 55 active targets in radiation pneumonia were identified. Subsequently, 137 candidate compounds and 469 Chinese herbs were matched. Frequency statistics showed that the Chinese herbs that could interfere with radiation pneumonia were mainly bitter, spicy, and sweet, with both cold and warm properties. Moreover, they mainly belonged to liver and lung channels. The core targets included TNF, IL-6, TGF-β1, and TP53. The most important components were quercetin, resveratrol, and (-)-epigallocatechin-3-gallate. Moreover, the most significant traditional Chinese herbs were Perilla pueraria, ephedra, Lonicerae japonicae, and sea buckthorn. Furthermore, analysis of 222 sets of receptor-ligand docking results suggested that the compounds had good docking activity to their core targets. By combining the docking binding energy, we determined that the chemical compounds had strong binding energy to the targets. Conclusion. Using network pharmacology, we explored the potential mechanism of TCM in the treatment of radiation pneumonia. The general rules for application of TCM in the treatment of radiation pneumonia were summarized. This study provides baseline information for future research on the development of TCM for the management of radiation pneumonia.

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“…The keyword “ischemic stroke” was used to search disease targets in the GeneCards database ( https://www.genecards.org/ ) ( Safran et al, 2021 ). According to the principles of TCM, the main symptoms of ischemic stroke with Qi deficiency and blood stasis syndrome are a pale white complexion, a shortness of breath, palpitations, spontaneous sweating, loose stools, limb swelling, angular salivation, a purple tongue, a thin and whitish tongue coating, and a deep and faint pulse.…”

Section: Methodsmentioning

confidence: 99%

A Network-Based Approach to Investigate the Neuroprotective Effects and Mechanisms of Action of Huangqi-Chuanxiong and Sanleng-Ezhu Herb Pairs in the Treatment of Cerebral Ischemic Stroke

et al. 2022

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Objective: We aimed to investigate the effect and mechanisms of action of two drug pairs [Huangqi-Chuanxiong and Sanleng-Ezhu Herb (HCSE)] on the treatment of ischemic stroke.Materials and methods: We mined the current literature related to ischemic stroke and formulated a new formulation of Chinese herbs. Then, we identified the main candidate target genes of the new formulation by network pharmacology. Next, we performed enrichment analysis of the target genes to identify the potential mechanism of action of the new formulation in the treatment of ischemic stroke. Next, we experimentally validated the mechanism of action of the new formulation against ischemic stroke. Infarct volume and neurological deficits were evaluated by 2,3,5-triphenyltetrazolium (TTC) staining and Longa’s score, respectively. The predicted pathways of signal-related proteins were detected by western blotting.Results: We mined the current literature and identified a new formulation of Chinese herbs for the treatment of ischemic stroke. The formulation included Huangqi, Chuanxiong, Sanleng and Ezhu. Next, we used network pharmacological analysis to identify 23 active compounds and 327 target genes for the new formulation. The key target genes were MAPK3, MAPK1, HSP90AA1, STAT3, PIK3R1, PIK3CA and AKT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant enrichment of the PI3K/AKT and MAPK/ERK signaling pathways. By performing experiments, we found that the new formulation reduced the infarct volume of middle cerebral artery occlusion (MCAO) induced mice and activated the PI3K/AKT and MAPK/ERK signaling pathways. These findings confirmed that the new formulation has a significant protective effect against ischemic stroke injury by activating the PI3K/AKT and MAPK/ERK signaling pathways.Conclusion: We identified a new treatment formulation for ischemic stroke by data mining and network pharmacological target prediction. The beneficial effects of the new formulation act by regulating multiple target genes and pathways. The mechanism of action of the new formulation may be related to the AKT and ERK signaling pathways. Our findings provide a theoretical basis for the effects of the new formulation on ischemic stroke injury.

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The GeneCards Suite

Cited by 350 publications

References 81 publications

Improved detection of evolutionary selection highlights potential bias from different sequencing strategies in complex genomic-regions

Improved detection of evolutionary selection highlights potential bias from different sequencing strategies in complex genomic-regions

Rules of Chinese Herbal Intervention of Radiation Pneumonia Based on Network Pharmacology and Data Mining

A Network-Based Approach to Investigate the Neuroprotective Effects and Mechanisms of Action of Huangqi-Chuanxiong and Sanleng-Ezhu Herb Pairs in the Treatment of Cerebral Ischemic Stroke

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