Pharmacogenomics Journal最新文献_第10页

Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis 希腊银屑病患者环孢素治疗反应药物遗传学研究中的蛋白质网络和通路分析

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-10-13 DOI: 10.1038/s41397-022-00291-7

Charalabos Antonatos, Aikaterini Patsatsi, Efterpi Zafiriou, Eleana F. Stavrou, Andreas Liaropoulos, Aikaterini Kyriakoy, Evangelos Evangelou, Danai Digka, Angeliki Roussaki-Schulze, Dimitris Sotiriadis, Sophia Georgiou, Katerina Grafanaki, Nicholas Κ. Moschonas, Yiannis Vasilopoulos

{"title":"Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis","authors":"Charalabos Antonatos, Aikaterini Patsatsi, Efterpi Zafiriou, Eleana F. Stavrou, Andreas Liaropoulos, Aikaterini Kyriakoy, Evangelos Evangelou, Danai Digka, Angeliki Roussaki-Schulze, Dimitris Sotiriadis, Sophia Georgiou, Katerina Grafanaki, Nicholas Κ. Moschonas, Yiannis Vasilopoulos","doi":"10.1038/s41397-022-00291-7","DOIUrl":"10.1038/s41397-022-00291-7","url":null,"abstract":"Although cyclosporine comprises a well-established systemic therapy for psoriasis, patients show important heterogeneity in their treatment response. The aim of our study was the pharmacogenetic analysis of 200 Greek patients with psoriasis based on the cyclosporine pathway related protein-protein interaction (PPI) network, reconstructed through the PICKLE meta-database. We genotyped 27 single nucleotide polymorphisms, mapped to 22 key protein nodes of the cyclosporine pathway, via the utilization of the iPLEX®GOLD panel of the MassARRAY® System. Single-SNP analyses showed statistically significant associations between CALM1 rs12885713 (P = 0.0108) and MALT1 rs2874116 (P = 0.0006) polymorphisms with positive response to cyclosporine therapy after correction for multiple comparisons, with the haplotype analyses further enhancing the predictive value of rs12885713 as a pharmacogenetic biomarker for cyclosporine therapy (P = 0.0173). Our findings have the potential to improve our prediction of cyclosporine efficacy and safety in psoriasis patients, as well as provide the framework for the pharmacogenetics of biological therapies in complex diseases.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"23 1","pages":"8-13"},"PeriodicalIF":2.8,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10850066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach 药物基因与 COVID-19 表现的关联：一种数据挖掘和网络生物学方法

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-28 DOI: 10.1038/s41397-022-00289-1

Theodosia Charitou, Panagiota I. Kontou, Ioannis A. Tamposis, Georgios A. Pavlopoulos, Georgia G. Braliou, Pantelis G. Bagos

{"title":"Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach","authors":"Theodosia Charitou, Panagiota I. Kontou, Ioannis A. Tamposis, Georgios A. Pavlopoulos, Georgia G. Braliou, Pantelis G. Bagos","doi":"10.1038/s41397-022-00289-1","DOIUrl":"10.1038/s41397-022-00289-1","url":null,"abstract":"Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"294-302"},"PeriodicalIF":2.8,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Publisher Correction: Cyrius: accurate CYP2D6 genotyping using whole-genome sequencing data 出版商更正：Cyrius：利用全基因组测序数据准确进行CYP2D6基因分型

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-28 DOI: 10.1038/s41397-022-00287-3

Xiao Chen, Fei Shen, Nina Gonzaludo, Alka Malhotra, Cande Rogert, Ryan J. Taft, David R. Bentley, Michael A. Eberle

引用次数: 0

The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data 主要药物代谢细胞色素 P450 基因的遗传格局--对群体规模测序数据的最新分析

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-09-06 DOI: 10.1038/s41397-022-00288-2

Yitian Zhou, Volker M. Lauschke

{"title":"The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data","authors":"Yitian Zhou, Volker M. Lauschke","doi":"10.1038/s41397-022-00288-2","DOIUrl":"10.1038/s41397-022-00288-2","url":null,"abstract":"Genes encoding cytochrome P450 enzymes (CYPs) are extremely polymorphic and multiple CYP variants constitute clinically relevant biomarkers for the guidance of drug selection and dosing. We previously reported the distribution of the most relevant CYP alleles using population-scale sequencing data. Here, we update these findings by making use of the increasing wealth of data, incorporating whole exome and whole genome sequencing data from 141,614 unrelated individuals across 12 human populations. We furthermore extend our previous studies by systematically considering also uncharacterized rare alleles and reveal that they contribute between 1.5% and 17.5% to the overall genetically encoded functional variability. By using established guidelines, we aggregate and translate the available sequencing data into population-specific patterns of metabolizer phenotypes. Combined, the presented data refine the worldwide landscape of ethnogeographic variability in CYP genes and aspire to provide a relevant resource for the optimization of population-specific genotyping strategies and precision public health.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"284-293"},"PeriodicalIF":2.8,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data 为全面的临床药理基因组学分析开发广泛的工作流程：从 100 个全外显子组测序数据的试点研究中汲取的经验教训

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-08-13 DOI: 10.1038/s41397-022-00286-4

Alireza Tafazoli, Maaike van der Lee, Jesse J. Swen, Anna Zeller, Natalia Wawrusiewicz-Kurylonek, Hailiang Mei, Ruben H. P. Vorderman, Krzysztof Konopko, Andrzej Zankiewicz, Wojciech Miltyk

{"title":"Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data","authors":"Alireza Tafazoli, Maaike van der Lee, Jesse J. Swen, Anna Zeller, Natalia Wawrusiewicz-Kurylonek, Hailiang Mei, Ruben H. P. Vorderman, Krzysztof Konopko, Andrzej Zankiewicz, Wojciech Miltyk","doi":"10.1038/s41397-022-00286-4","DOIUrl":"10.1038/s41397-022-00286-4","url":null,"abstract":"This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45–70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"276-283"},"PeriodicalIF":2.8,"publicationDate":"2022-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40720493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

A blockchain-based framework to support pharmacogenetic data sharing 支持药物基因数据共享的区块链框架

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-07-22 DOI: 10.1038/s41397-022-00285-5

F. Albalwy, J. H. McDermott, W. G. Newman, A. Brass, A. Davies

{"title":"A blockchain-based framework to support pharmacogenetic data sharing","authors":"F. Albalwy, J. H. McDermott, W. G. Newman, A. Brass, A. Davies","doi":"10.1038/s41397-022-00285-5","DOIUrl":"10.1038/s41397-022-00285-5","url":null,"abstract":"The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain’s performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 5-6","pages":"264-275"},"PeriodicalIF":2.8,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals 与临床相关的 CYP2C8*3 和 CYP2C9*2 单倍型是从尼安德特人那里遗传的

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-07-02 DOI: 10.1038/s41397-022-00284-6

Sigrid Haeggström, Magnus Ingelman-Sundberg, Svante Pääbo, Hugo Zeberg

引用次数: 2

A machine learning model using SNPs obtained from a genome-wide association study predicts the onset of vincristine-induced peripheral neuropathy 利用从全基因组关联研究中获得的 SNPs 的机器学习模型预测长春新碱诱发的周围神经病变的发病情况

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-06-25 DOI: 10.1038/s41397-022-00282-8

Hiroki Yamada, Rio Ohmori, Naoto Okada, Shingen Nakamura, Kumiko Kagawa, Shiro Fujii, Hirokazu Miki, Keisuke Ishizawa, Masahiro Abe, Youichi Sato

{"title":"A machine learning model using SNPs obtained from a genome-wide association study predicts the onset of vincristine-induced peripheral neuropathy","authors":"Hiroki Yamada, Rio Ohmori, Naoto Okada, Shingen Nakamura, Kumiko Kagawa, Shiro Fujii, Hirokazu Miki, Keisuke Ishizawa, Masahiro Abe, Youichi Sato","doi":"10.1038/s41397-022-00282-8","DOIUrl":"10.1038/s41397-022-00282-8","url":null,"abstract":"Vincristine treatment may cause peripheral neuropathy. In this study, we identified the genes associated with the development of peripheral neuropathy due to vincristine therapy using a genome-wide association study (GWAS) and constructed a predictive model for the development of peripheral neuropathy using genetic information-based machine learning. The study included 72 patients admitted to the Department of Hematology, Tokushima University Hospital, who received vincristine. Of these, 56 were genotyped using the Illumina Asian Screening Array-24 Kit, and a GWAS for the onset of peripheral neuropathy caused by vincristine was conducted. Using Sanger sequencing for 16 validation samples, the top three single nucleotide polymorphisms (SNPs) associated with the onset of peripheral neuropathy were determined. Machine learning was performed using the statistical software R package “caret”. The 56 GWAS and 16 validation samples were used as the training and test sets, respectively. Predictive models were constructed using random forest, support vector machine, naive Bayes, and neural network algorithms. According to the GWAS, rs2110179, rs7126100, and rs2076549 were associated with the development of peripheral neuropathy on vincristine administration. Machine learning was performed using these three SNPs to construct a prediction model. A high accuracy of 93.8% was obtained with the support vector machine and neural network using rs2110179 and rs2076549. Thus, peripheral neuropathy development due to vincristine therapy can be effectively predicted by a machine learning prediction model using SNPs associated with it.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 4","pages":"241-246"},"PeriodicalIF":2.8,"publicationDate":"2022-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40398491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders miRNA 作为精神疾病的潜在诊断生物标志物和药物基因组学指标

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-06-20 DOI: 10.1038/s41397-022-00283-7

Evangelia Eirini Tsermpini, Christina I. Kalogirou, George C. Kyriakopoulos, George P. Patrinos, Constantinos Stathopoulos

{"title":"miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders","authors":"Evangelia Eirini Tsermpini, Christina I. Kalogirou, George C. Kyriakopoulos, George P. Patrinos, Constantinos Stathopoulos","doi":"10.1038/s41397-022-00283-7","DOIUrl":"10.1038/s41397-022-00283-7","url":null,"abstract":"The heterogeneity of psychiatric disorders and the lack of reliable biomarkers for prediction and treatments follow-up pose difficulties towards recognition and understanding of the molecular basis of psychiatric diseases. However, several studies based on NGS approaches have shown that miRNAs could regulate gene expression during onset and disease progression and could serve as potential diagnostic and pharmacogenomics biomarkers during treatment. We provide herein a detailed overview of circulating miRNAs and their expression profiles as biomarkers in schizophrenia, bipolar disorder and major depressive disorder and their role in response to specific treatments. Bioinformatics analysis of miR-34a, miR-106, miR-134 and miR-132, which are common among SZ, BD and MDD patients, showed brain enrichment and involvement in the modulation of critical signaling pathways, which are often deregulated in psychiatric disorders. We propose that specific miRNAs support accurate diagnosis and effective precision treatment of psychiatric disorders.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 4","pages":"211-222"},"PeriodicalIF":2.8,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40104450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis 氯氮平诱导的粒细胞缺乏症的药物基因组学:系统回顾和荟萃分析

IF 2.8 3区医学

Pharmacogenomics Journal Pub Date : 2022-06-16 DOI: 10.1038/s41397-022-00281-9

Farhana Islam, Daniel Hain, David Lewis, Rebecca Law, Lisa C. Brown, Julie-Anne Tanner, Daniel J. Müller

{"title":"Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis","authors":"Farhana Islam, Daniel Hain, David Lewis, Rebecca Law, Lisa C. Brown, Julie-Anne Tanner, Daniel J. Müller","doi":"10.1038/s41397-022-00281-9","DOIUrl":"10.1038/s41397-022-00281-9","url":null,"abstract":"Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20–15.80, pcorrected = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"22 4","pages":"230-240"},"PeriodicalIF":2.8,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-022-00281-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41484995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6