Finding commonalities in rare diseases through the undiagnosed diseases network.
Finding commonalities in rare diseases through the undiagnosed diseases network.
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通过未诊断疾病网络寻找罕见疾病的共性。
DOI：
10.1093/jamia/ocab050
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发表时间：
2021-07-30
期刊：
影响因子：
--
通讯作者：
Avillach P
中科院分区：
文献类型：
--
作者：
Yates J;Gutiérrez-Sacristán A;Jouhet V;LeBlanc K;Esteves C;Undiagnosed Diseases Network;DeSain TN;Benik N;Stedman J;Palmer N;Mellon G;Kohane I;Avillach P
在研究任何特定的罕见疾病时，受影响个体的异质性和稀缺性历来阻碍研究人员辨别出应该关注什么来了解和诊断一种疾病。必须开发新的非基因组方法，在看似不同的条件下识别相似之处。这项观察性研究分析了来自未诊断疾病网络(2015-2019年)的1042名患者，这是一项多中心的全国性研究，使用由专业人员使用人类表型本体术语注释的表型数据。我们使用Louvain群落检测对Jaccard成对相似性关联的患者进行聚类，并使用2个支持向量分类器来分配新病例。我们使用国家索赔数据库(6700万患者)进一步验证了集群中最具代表性的合并症。患者分为两组：18岁前起病组(n = 810)和18岁以上组(n = 2 32)(平均起病年龄10[四分位数范围0~14]岁)。对于810名儿科患者，我们确定了4个具有统计学意义的簇。有两组患者以生长障碍为特征，而发育迟缓表现为低眼压表现出更高的诊断可能性。支持向量分类器在测试数据上显示了0.89的均衡准确率(仅对人类表型本体论术语为0.83)。为了为将来的发现设定框架，我们选择了成功的按表型相似性对患者进行分组作为我们的终点，并提供了一个分类工具来将新患者分配到这些分组。这项研究表明，尽管患者的稀缺性和异质性，我们仍然可以找到潜在的共性，以发现新的见解和治疗目标。
When studying any specific rare disease, heterogeneity and scarcity of affected individuals has historically hindered investigators from discerning on what to focus to understand and diagnose a disease. New nongenomic methodologies must be developed that identify similarities in seemingly dissimilar conditions. This observational study analyzes 1042 patients from the Undiagnosed Diseases Network (2015-2019), a multicenter, nationwide research study using phenotypic data annotated by specialized staff using Human Phenotype Ontology terms. We used Louvain community detection to cluster patients linked by Jaccard pairwise similarity and 2 support vector classifier to assign new cases. We further validated the clusters’ most representative comorbidities using a national claims database (67 million patients). Patients were divided into 2 groups: those with symptom onset before 18 years of age (n = 810) and at 18 years of age or older (n = 232) (average symptom onset age: 10 [interquartile range, 0-14] years). For 810 pediatric patients, we identified 4 statistically significant clusters. Two clusters were characterized by growth disorders, and developmental delay enriched for hypotonia presented a higher likelihood of diagnosis. Support vector classifier showed 0.89 balanced accuracy (0.83 for Human Phenotype Ontology terms only) on test data. To set the framework for future discovery, we chose as our endpoint the successful grouping of patients by phenotypic similarity and provide a classification tool to assign new patients to those clusters. This study shows that despite the scarcity and heterogeneity of patients, we can still find commonalities that can potentially be harnessed to uncover new insights and targets for therapy.
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影响因子：
4.1
作者：
Fernandez-Marmiesse A;Gouveia S;Couce ML
通讯作者：
Couce ML
DOI：
10.1126/science.aal4043
发表时间：
2018-03-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastarache L;Hughey JJ;Hebbring S;Marlo J;Zhao W;Ho WT;Van Driest SL;McGregor TL;Mosley JD;Wells QS;Temple M;Ramirez AH;Carroll R;Osterman T;Edwards T;Ruderfer D;Velez Edwards DR;Hamid R;Cogan J;Glazer A;Wei WQ;Feng Q;Brilliant M;Zhao ZJ;Cox NJ;Roden DM;Denny JC
通讯作者：
Denny JC
影响因子：
14.9
作者：
Köhler S;Vasilevsky NA;Engelstad M;Foster E;McMurry J;Aymé S;Baynam G;Bello SM;Boerkoel CF;Boycott KM;Brudno M;Buske OJ;Chinnery PF;Cipriani V;Connell LE;Dawkins HJ;DeMare LE;Devereau AD;de Vries BB;Firth HV;Freson K;Greene D;Hamosh A;Helbig I;Hum C;Jähn JA;James R;Krause R;F Laulederkind SJ;Lochmüller H;Lyon GJ;Ogishima S;Olry A;Ouwehand WH;Pontikos N;Rath A;Schaefer F;Scott RH;Segal M;Sergouniotis PI;Sever R;Smith CL;Straub V;Thompson R;Turner C;Turro E;Veltman MW;Vulliamy T;Yu J;von Ziegenweidt J;Zankl A;Züchner S;Zemojtel T;Jacobsen JO;Groza T;Smedley D;Mungall CJ;Haendel M;Robinson PN
通讯作者：
Robinson PN
影响因子：
14.9
作者：
Köhler S;Gargano M;Matentzoglu N;Carmody LC;Lewis-Smith D;Vasilevsky NA;Danis D;Balagura G;Baynam G;Brower AM;Callahan TJ;Chute CG;Est JL;Galer PD;Ganesan S;Griese M;Haimel M;Pazmandi J;Hanauer M;Harris NL;Hartnett MJ;Hastreiter M;Hauck F;He Y;Jeske T;Kearney H;Kindle G;Klein C;Knoflach K;Krause R;Lagorce D;McMurry JA;Miller JA;Munoz-Torres MC;Peters RL;Rapp CK;Rath AM;Rind SA;Rosenberg AZ;Segal MM;Seidel MG;Smedley D;Talmy T;Thomas Y;Wiafe SA;Xian J;Yüksel Z;Helbig I;Mungall CJ;Haendel MA;Robinson PN
通讯作者：
Robinson PN
DOI：
10.1002/ajmg.b.32579
发表时间：
2018-10
期刊：
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
影响因子：
--
作者：
Kothari C;Wack M;Hassen-Khodja C;Finan S;Savova G;O'Boyle M;Bliss G;Cornell A;Horn EJ;Davis R;Jacobs J;Kohane I;Avillach P
通讯作者：
Avillach P