scholarly journals AMELIE accelerates Mendelian patient diagnosis directly from the primary literature

2017 ◽  
Author(s):  
Johannes Birgmeier ◽  
Maximilian Haeussler ◽  
Cole A. Deisseroth ◽  
Karthik A. Jagadeesh ◽  
Alexander J. Ratner ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Current Data ◽  
Causal Gene ◽  
Gene Ranking ◽  
Literature Research ◽  
Mendelian Disorders ◽  
Functional Variants ◽  
Patient Diagnosis ◽  
Primary Literature ◽  
Identical Performance

AbstractThe diagnosis of Mendelian disorders requires labor-intensive literature research. Our software system AMELIE (Automatic Mendelian Literature Evaluation) greatly automates this process. AMELIE parses hundreds of thousands of full text articles to find an underlying diagnosis to explain a patient’s phenotypes given the patient’s exome. AMELIE prioritizes patient candidate genes for their likelihood of causing the patient’s phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario. AMELIE’s gene ranking method was tested on 215 singleton Mendelian patients with a clinical diagnosis. AMELIE ranked the causal gene among the top 2 in the majority (63%) of cases. Examining AMELIE’s top 10 genes, amounting to 8% of 124 candidate genes with rare functional variants per patient, results in diagnosis for 95% of cases. Strikingly, training only on gene pathogenicity knowledge from 2011 leads to identical performance compared to training on current data. An accompanying analysis web portal has launched at AMELIE.stanford.edu.

scholarly journals Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders

2021 ◽  
Author(s):  
Yi Zhang ◽  
Tao Wang ◽  
Yan Wang ◽  
Kun Xia ◽  
Jinchen Li ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Neurodevelopmental Disorders ◽  
De Novo ◽  
Genetic Data ◽  
Chinese Patients ◽  
The Novel ◽  
Mutational Spectrum ◽  
Functional Variants ◽  
Public Data ◽  
Chromosomal Genes

AbstractNeurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.

Analysis of functional variants reveals new candidate genes associated with alexithymia

2015 ◽  
Vol 227 (2-3) ◽  
pp. 363-365 ◽  
Author(s):  
Massimo Mezzavilla ◽  
Sheila Ulivi ◽  
Martina La Bianca ◽  
Davide Carlino ◽  
Paolo Gasparini ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Functional Variants

Candidate genes for schizophrenia: A survey of association studies and gene ranking

2008 ◽  
Vol 147B (7) ◽  
pp. 1173-1181 ◽  
Author(s):  
Jingchun Sun ◽  
Po-Hsiu Kuo ◽  
Brien P. Riley ◽  
Kenneth S. Kendler ◽  
Zhongming Zhao
Keyword(s):  
Candidate Genes ◽  
Association Studies ◽  
Gene Ranking

66 A DIRECT HAPLOTYPING METHOD OF PUTATIVE FUNCTIONAL VARIANTS IN PROMOTER REGIONS OF THREE CANDIDATE GENES IN ACUTE LUNG INJURY.

2006 ◽  
Vol 54 (2) ◽  
pp. S354.4-S354
Author(s):  
M. M. Kalscheur ◽  
C. Flores ◽  
S. F. Ma ◽  
M. Burke ◽  
W. J. Buikema ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Candidate Genes ◽  
Promoter Regions ◽  
Functional Variants

scholarly journals Rare functional variants in genome-wide association identified candidate genes for nonsyndromic clefts in the African population

2014 ◽  
Vol 164 (10) ◽  
pp. 2567-2571 ◽  
Author(s):  
Azeez Butali ◽  
Peter Mossey ◽  
Wasiu Adeyemo ◽  
Mekonen Eshete ◽  
Lauren Gaines ◽  
...  
Keyword(s):  
Candidate Genes ◽  
African Population ◽  
Genome Wide Association ◽  
Functional Variants ◽  
Genome Wide

scholarly journals Indoor phytoremediation using decorative plants: An overview of application principles

2021 ◽  
pp. 28-32
Author(s):  
Harida Samudro ◽  
Sarwoko Mangkoedihardjo
Keyword(s):  
Green Building ◽  
Current Data ◽  
Literature Research ◽  
Indoor Space ◽  
Natural Approach ◽  
Important Concern ◽  
Main Target ◽  
Study Methodology ◽  
Indoor Spaces ◽  
Selection Of

A healthy and sustainable indoor space was one of the goals of a building, which was an important concern of architects in designing and using it. Design arrangements can be approached physically, such as the use of air vents, lighting, and layout arrangements. However, now the paradigm of using a natural approach has been intensive. In this regard, this paper focuses on the greening of indoor spaces, both for the prevention and restoration of indoor room quality. The study methodology was a survey of existing research results in many countries, and a selection of up-to-date, current data. The results of the literature research obtained are related to the purpose of indoor greening, which is none other than to achieve the goal of green building. Its main target was biodiversity in the prevention of negative health effects and indoor phytoremediation.

scholarly journals AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature

2020 ◽  
Vol 12 (544) ◽  
pp. eaau9113 ◽  
Author(s):  
Johannes Birgmeier ◽  
Maximilian Haeussler ◽  
Cole A. Deisseroth ◽  
Ethan H. Steinberg ◽  
Karthik A. Jagadeesh ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Retrospective Cohort ◽  
Developmental Disorders ◽  
Single Gene ◽  
Rapid Diagnosis ◽  
Causative Gene ◽  
Mendelian Disorders ◽  
Disease Research ◽  
Primary Literature ◽  
The Right

The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication(s) supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts and downloads and further parses hundreds of thousands of full-text articles in search of information supporting the causality and associated phenotypes of most published genetic variants. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario, and AMELIE ranked the causative gene at the very top for 66% of 215 diagnosed singleton Mendelian patients from the Deciphering Developmental Disorders project. Evaluating only the top 11 AMELIE-scored genes of 127 (median) candidate genes per patient resulted in a rapid diagnosis in more than 90% of cases. AMELIE-based evaluation of all cases was 3 to 19 times more efficient than hand-curated database–based approaches. We replicated these results on a retrospective cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface, and code is available at AMELIE.stanford.edu.

scholarly journals A multiple-causal-gene-cluster model underlying GWAS signals of Alzheimer's disease

2021 ◽  
Author(s):  
Min Xu ◽  
Qianjin Liu ◽  
Rui Bi ◽  
Yu Li ◽  
Chunhua Zeng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Cluster ◽  
Cluster Model ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Biological Mechanisms ◽  
Causal Gene ◽  
Functional Variants ◽  
Causal Genes

Genome-wide association studies (GWASs) have identified dozens of genetic susceptibility loci for Alzheimer's disease (AD). Nevertheless, the underlying causal variants and biological mechanisms remain elusive. Here, we systematically integrated AD GWAS with comprehensive multi-omics data, and distilled 304 potentially functional variants and 166 causal genes from 49 loci. Intriguingly, we found that most of AD GWAS loci contain multiple functional variants and causal genes. In vitro assays showed that one functional variant regulated multiple genes in the 11p11.2 locus (the CELF1/SPI1 locus) and alteration of these target genes contributed to AD-related molecular processes, supporting the co-existence of multiple functional variants and AD-relevant causal genes within a single locus. We thus proposed a multiple-causal-gene-cluster model that co-dysregulation of a cluster of genes within a single GWAS loci individually or synergistically contribute to AD development. This model provides a novel insight into the biological mechanisms underlying the GWAS loci of complex traits.

Targeted Sequencing and Integrative Analysis to Prioritise Candidate Genes in Neurodevelopmental Disorders

2021 ◽  
Author(s):  
Yi Zhang ◽  
Tao Wang ◽  
Yan Wang ◽  
Kun Xia ◽  
Jinchen Li ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Neurodevelopmental Disorders ◽  
De Novo ◽  
Genetic Data ◽  
Chinese Patients ◽  
The Novel ◽  
Mutational Spectrum ◽  
Functional Variants ◽  
Public Data ◽  
Chromosomal Genes

Abstract Neurodevelopmental disorders (NDDs) are a group of diseases characterized by highly heterogeneity and frequently co-occur symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1,102 patients with NDDs and validated 1,271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritised 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was most frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritises 212 NDD candidate genes for further functional validation and genetic counseling.

scholarly journals A targeted genotyping approach to enhance the identification of variants for lactation persistency in dairy cows

2019 ◽  
Vol 97 (10) ◽  
pp. 4066-4075
Author(s):  
Duy Ngoc Do ◽  
Nathalie Bissonnette ◽  
Pierre Lacasse ◽  
Filippo Miglior ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Mixed Model ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genetic Selection ◽  
Phenotypic Variance ◽  
Potential Candidate ◽  
Nucleotide Polymorphisms ◽  
Functional Variants ◽  
Selection For

Abstract Lactation persistency (LP), defined as the ability of a cow to maintain milk production at a high level after milk peak, is an important phenotype for the dairy industry. In this study, we used a targeted genotyping approach to scan for potentially functional single nucleotide polymorphisms (SNPs) within 57 potential candidate genes derived from our previous genome wide association study on LP and from the literature. A total of 175,490 SNPs were annotated within 10-kb flanking regions of the selected candidate genes. After applying several filtering steps, a total of 105 SNPs were retained for genotyping using target genotyping arrays. SNP association analyses were performed in 1,231 Holstein cows with 69 polymorphic SNPs using the univariate liner mixed model with polygenic effects using DMU package. Six SNPs including rs43770847, rs208794152, and rs208332214 in ADRM1; rs209443540 in C5orf34; rs378943586 in DDX11; and rs385640152 in GHR were suggestively significantly associated with LP based on additive effects and associations with 4 of them (rs43770847, rs208794152, rs208332214, and rs209443540) were based on dominance effects at P < 0.05. However, none of the associations remained significant at false discovery rate adjusted P (FDR) < 0.05. The additive variances explained by each suggestively significantly associated SNP ranged from 0.15% (rs43770847 in ADRM1) to 5.69% (rs209443540 in C5orf34), suggesting that these SNPs might be used in genetic selection for enhanced LP. The percentage of phenotypic variance explained by dominance effect ranged from 0.24% to 1.35% which suggests that genetic selection for enhanced LP might be more efficient by inclusion of dominance effects. Overall, this study identified several potentially functional variants that might be useful for selection programs for higher LP. Finally, a combination of identification of potentially functional variants followed by targeted genotyping and association analysis is a cost-effective approach for increasing the power of genetic association studies.

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