Articles

Strategies to minimize false positives and interpret novel microdeletions based on maternal copy-number variants in 87,000 noninvasive prenatal screens

Noninvasive prenatal screening (NIPS) of common aneuploidies using cell-free DNA from maternal plasma is part of routine prenatal care and is widely used in both high-risk and low-risk patient populations. Hig...

Authors: Kristjan Eerik Kaseniit, Gregory J Hogan, Kevin M D’Auria, Carrie Haverty and Dale Muzzey

Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Nuclear genes or family-based mitochondrial screening have been the focus of genetic studies into essential hypertension. Studies into the role of mitochondria in sporadic Chinese hypertensives are lacking. Th...

Authors: Ye Zhu, Xiang Gu and Chao Xu

Privacy-preserving logistic regression training

Logistic regression is a popular technique used in machine learning to construct classification models. Since the construction of such models is based on computing with large datasets, it is an appealing idea ...

Authors: Charlotte Bonte and Frederik Vercauteren

iDASH secure genome analysis competition 2017

Authors: XiaoFeng Wang, Haixu Tang, Shuang Wang, Xiaoqian Jiang, Wenhao Wang, Diyue Bu, Lei Wang, Yicheng Jiang and Chenghong Wang

Privacy-preserving record linkage in large databases using secure multiparty computation

Practical applications for data analysis may require combining multiple databases belonging to different owners, such as health centers. The analysis should be performed without violating privacy of neither th...

Authors: Peeter Laud and Alisa Pankova

Logistic regression model training based on the approximate homomorphic encryption

Security concerns have been raised since big data became a prominent tool in data analysis. For instance, many machine learning algorithms aim to generate prediction models using training data which contain se...

Authors: Andrey Kim, Yongsoo Song, Miran Kim, Keewoo Lee and Jung Hee Cheon

Secure top most significant genome variants search: iDASH 2017 competition

One of the 3 tracks of iDASH Privacy & Security Workshop 2017 competition was to execute a whole genome variants search on private genomic data. Particularly, the search application was to find the top most si...

Authors: Sergiu Carpov and Thibaud Tortech

Logistic regression over encrypted data from fully homomorphic encryption

One of the tasks in the 2017 iDASH secure genome analysis competition was to enable training of logistic regression models over encrypted genomic data. More precisely, given a list of approximately 1500 patien...

Authors: Hao Chen, Ran Gilad-Bachrach, Kyoohyung Han, Zhicong Huang, Amir Jalali, Kim Laine and Kristin Lauter

Genomics of drug sensitivity in bladder cancer: an integrated resource for pharmacogenomic analysis in bladder cancer

Bladder cancer has numerous genomic features that are potentially actionable by targeted agents. Nevertheless, both pre-clinical and clinical research using molecular targeted agents have been very limited in ...

Authors: Adnan Ahmad Ansari, Inkeun Park, Inki Kim, Sojung Park, Sung-Min Ahn and Jae-lyun Lee

New insights into the phenotypic spectrum of 14q22q23 deletions: a case report and literature review

Mutations occurring in the orthodenticle homeobox 2 gene (OTX2) are responsible for a rare genetic syndrome, characterized mainly by microphthalmia/anophthalmia associated with extra-ocular defects such as brain ...

Authors: Anna Pichiecchio, Giovanni Vitale, Camilla Caporali, Cecilia Parazzini, Donatella Milani, Maria Paola Recalcati, Laura D’Amico, Sabrina Signorini, Umberto Balottin and Stefano Bastianello

Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers

The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS...

Authors: Silke Schultz, Harald Bartsch, Karl Sotlar, Karina Petat-Dutter, Michael Bonin, Steffen Kahlert, Nadia Harbeck, Ulrich Vogel, Harald Seeger, Tanja Fehm and Hans J. Neubauer

Rare variants in the splicing regulatory elements of EXOC3L4 are associated with brain glucose metabolism in Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases that causes problems related to brain function. To some extent it is understood on a molecular level how AD arises, however there a...

Authors: Jason E. Miller, Manu K. Shivakumar, Younghee Lee, Seonggyun Han, Emrin Horgousluoglu, Shannon L. Risacher, Andrew J. Saykin, Kwangsik Nho and Dokyoon Kim

Pathway networks generated from human disease phenome

Understanding the effect of human genetic variations on disease can provide insight into phenotype-genotype relationships, and has great potential for improving the effectiveness of personalized medicine. Whil...

Authors: Ann G. Cirincione, Kaylyn L. Clark and Maricel G. Kann

Min-redundancy and max-relevance multi-view feature selection for predicting ovarian cancer survival using multi-omics data

Large-scale collaborative precision medicine initiatives (e.g., The Cancer Genome Atlas (TCGA)) are yielding rich multi-omics data. Integrative analyses of the resulting multi-omics data, such as somatic mutat...

Authors: Yasser EL-Manzalawy, Tsung-Yu Hsieh, Manu Shivakumar, Dokyoon Kim and Vasant Honavar

Local genetic ancestry in CDKN2B-AS1 is associated with primary open-angle glaucoma in an African American cohort extracted from de-identified electronic health records

Glaucoma is a leading cause of blindness in developed countries. Primary open-angle glaucoma (POAG), the most prevalent clinical subtype of glaucoma in the United States, affects African Americans at a higher ...

Authors: Nicole A. Restrepo, Sarah M. Laper, Eric Farber-Eger and Dana C. Crawford

Integrative pathway-based survival prediction utilizing the interaction between gene expression and DNA methylation in breast cancer

Integrative analysis on multi-omics data has gained much attention recently. To investigate the interactive effect of gene expression and DNA methylation on cancer, we propose a directed random walk-based appr...

Authors: So Yeon Kim, Tae Rim Kim, Hyun-Hwan Jeong and Kyung-Ah Sohn

Indel sensitive and comprehensive variant/mutation detection from RNA sequencing data for precision medicine

RNA-seq is the most commonly used sequencing application. Not only does it measure gene expression but it is also an excellent media to detect important structural variants such as single nucleotide variants (...

Authors: Naresh Prodduturi, Aditya Bhagwate, Jean-Pierre A. Kocher and Zhifu Sun

Frequency and phenotype consequence of APOC3 rare variants in patients with very low triglyceride levels

High levels of triglycerides (TG ≥200 mg/dL) are an emerging risk factor for cardiovascular disease. Conversely, very low levels of TG are associated with decreased risk for cardiovascular disease. Precision m...

Authors: Dana C. Crawford, Nicole A. Restrepo, Kirsten E. Diggins, Eric Farber-Eger and Quinn S. Wells

TAP: a targeted clinical genomics pipeline for detecting transcript variants using RNA-seq data

RNA-seq is a powerful and cost-effective technology for molecular diagnostics of cancer and other diseases, and it can reach its full potential when coupled with validated clinical-grade informatics tools. Des...

Authors: Readman Chiu, Ka Ming Nip, Justin Chu and Inanc Birol

Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling

CRISPR/CAS9 (epi)genome editing revolutionized the field of gene and cell therapy. Our previous study demonstrated that a rapid and robust reactivation of the HIV latent reservoir by a catalytically-deficient ...

Authors: Yonggang Zhang, Gustavo Arango, Fang Li, Xiao Xiao, Raj Putatunda, Jun Yu, Xiao-Feng Yang, Hong Wang, Layne T. Watson, Liqing Zhang and Wenhui Hu

Whole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes

Deafness is a highly heterogenous disorder with over 100 genes known to underlie human non-syndromic hearing impairment. However, many more remain undiscovered, particularly those involved in the most common f...

Authors: Morag A. Lewis, Lisa S. Nolan, Barbara A. Cadge, Lois J. Matthews, Bradley A. Schulte, Judy R. Dubno, Karen P. Steel and Sally J. Dawson

Correction to: The Cancer Omics Atlas: an integrative resource for cancer omics annotations

Following publication of the original article [1], the authors reported an error in Fig. 1A.

Authors: Qingrong Sun, Mengyuan Li and Xiaosheng Wang

Differentially expressed proteins in positive versus negative HNSCC lymph nodes

Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteri...

Authors: Alessandra Vidotto, Giovana M. Polachini, Marina de Paula-Silva, Sonia M. Oliani, Tiago Henrique, Rossana V. M. López, Patrícia M. Cury, Fabio D. Nunes, José F. Góis-Filho, Marcos B. de Carvalho, Andréia M. Leopoldino and Eloiza H. Tajara

Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line

Moyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Rece...

Authors: Haruto Uchino, Masaki Ito, Ken Kazumata, Yuka Hama, Shuji Hamauchi, Shunsuke Terasaka, Hidenao Sasaki and Kiyohiro Houkin

Multiple occurrence of psychomotor retardation and recurrent miscarriages in a family with a submicroscopic reciprocal translocation t(7;17)(p22;p13.2)

Balanced reciprocal chromosomal translocations (RCTs) are the ones of the most common structural aberrations in the population, with an incidence of 1:625. RCT carriers usually do not demonstrate changes in ph...

Authors: Magdalena Pasińska, Ewelina Łazarczyk, Katarzyna Jułga, Magdalena Bartnik-Głaska, Beata Nowakowska and Olga Haus

Additional germline findings from a tumor profiling program

Matched tumor-normal sequencing, applied in precision cancer medicine, can identify unidentified germline Medically Actionable Variants (gMAVS) in cancer predisposition genes. We report patient preferences for...

Authors: Neda Stjepanovic, Tracy L. Stockley, Philippe L. Bedard, Jeanna M. McCuaig, Melyssa Aronson, Spring Holter, Kara Semotiuk, Natasha B. Leighl, Raymond Jang, Monika K. Krzyzanowska, Amit M. Oza, Abha Gupta, Christine Elser, Lailah Ahmed, Lisa Wang, Suzanne Kamel-Reid…

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women

Gestational diabetes (GDM) is a more common problem in India than in many other parts of the world but it is not known whether this is due to unique environmental factors or a unique genetic background. To add...

Authors: Geeti P. Arora, Peter Almgren, Charlotte Brøns, Richa G. Thaman, Allan A. Vaag, Leif Groop and Rashmi B. Prasad

The Cancer Omics Atlas: an integrative resource for cancer omics annotations

The Cancer Genome Atlas (TCGA) is an important data resource for cancer biologists and oncologists. However, a lack of bioinformatics expertise often hinders experimental cancer biologists and oncologists from...

Authors: Qingrong Sun, Mengyuan Li and Xiaosheng Wang

Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis

Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear.

Authors: Madhusudan Grover, Simon J. Gibbons, Asha A. Nair, Cheryl E. Bernard, Adeel S. Zubair, Seth T. Eisenman, Laura A. Wilson, Laura Miriel, Pankaj J. Pasricha, Henry P. Parkman, Irene Sarosiek, Richard W. McCallum, Kenneth L. Koch, Thomas L. Abell, William J. Snape, Braden Kuo…

Longitudinal expression profiling of CD4+ and CD8+ cells in patients with active to quiescent giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging d...

Authors: Elisabeth De Smit, Samuel W. Lukowski, Lisa Anderson, Anne Senabouth, Kaisar Dauyey, Sharon Song, Bruce Wyse, Lawrie Wheeler, Christine Y. Chen, Khoa Cao, Amy Wong Ten Yuen, Neil Shuey, Linda Clarke, Isabel Lopez Sanchez, Sandy S. C. Hung, Alice Pébay…

Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report

The proto-oncogene KRAS performs an essential function in normal tissue signaling, and the mutation of KRAS gene is a key step in the development of many cancers. Somatic KRAS mutations are often detected in p...

Authors: Ruen Yao, Tingting Yu, Yufei Xu, Guoqiang Li, Lei Yin, Yunfang Zhou, Jian Wang and Zhilong Yan

Identification of differential gene expression profile from peripheral blood cells of military pilots with hypertension by RNA sequencing analysis

Elevated blood pressure is an important risk factor for cardiovascular disease and is also an important factor in global mortality. Military pilots are at high risk of cardiovascular disease because they under...

Authors: Xing-Cheng Zhao, Shao-Hua Yang, Yi-Quan Yan, Xin Zhang, Lin Zhang, Bo Jiao, Shuai Jiang and Zhi-Bin Yu

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accur...

Authors: Rubén Cabanillas, Marta Diñeiro, Guadalupe A. Cifuentes, David Castillo, Patricia C. Pruneda, Rebeca Álvarez, Noelia Sánchez-Durán, Raquel Capín, Ana Plasencia, Mónica Viejo-Díaz, Noelia García-González, Inés Hernando, José L. Llorente, Alfredo Repáraz-Andrade, Cristina Torreira-Banzas, Jordi Rosell…

Phenotype-driven gene prioritization for rare diseases using graph convolution on heterogeneous networks

One of the major goals of genomic medicine is the identification of causal genomic variants in a patient and their relation to the observed clinical phenotypes. Prioritizing the genomic variants by considering...

Authors: Aditya Rao, Saipradeep VG, Thomas Joseph, Sujatha Kotte, Naveen Sivadasan and Rajgopal Srinivasan

Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study

Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural...

Authors: Ting Yu, Lei Xia, Dan Bi, Yangong Wang, Qing Shang, Dengna Zhu, Juan Song, Yong Wang, Xiaoyang Wang, Changlian Zhu and Qinghe Xing

Blood pressure signature genes and blood pressure response to thiazide diuretics: results from the PEAR and PEAR-2 studies

Recently, 34 genes had been associated with differential expression relative to blood pressure (BP)/ hypertension (HTN). We hypothesize that some of the genes associated with BP/HTN are also associated with BP...

Authors: Ana Caroline C. Sá, Amy Webb, Yan Gong, Caitrin W. McDonough, Mohamed H. Shahin, Somnath Datta, Taimour Y. Langaee, Stephen T. Turner, Amber L. Beitelshees, Arlene B. Chapman, Eric Boerwinkle, John G. Gums, Steven E. Scherer, Rhonda M. Cooper-DeHoff, Wolfgang Sadee and Julie A. Johnson

Genetic interaction effects reveal lipid-metabolic and inflammatory pathways underlying common metabolic disease risks

Common metabolic diseases, including type 2 diabetes, coronary artery disease, and hypertension, arise from disruptions of the body’s metabolic homeostasis, with relatively strong contributions from genetic ri...

Authors: Hyung Jun Woo and Jaques Reifman

Calculating the statistical significance of rare variants causal for Mendelian and complex disorders

With the expanding use of next-gen sequencing (NGS) to diagnose the thousands of rare Mendelian genetic diseases, it is critical to be able to interpret individual DNA variation. To calculate the significance ...

Authors: Aliz R. Rao and Stanley F. Nelson

RNA sequencing-based longitudinal transcriptomic profiling gives novel insights into the disease mechanism of generalized pustular psoriasis

Generalized pustular psoriasis (GPP) is a rare, episodic, potentially life-threatening inflammatory disease. However, the pathogenesis of GPP, and universally accepted therapies for treating it, remain undefined.

Authors: Lingyan Wang, Xiaoling Yu, Chao Wu, Teng Zhu, Wenming Wang, Xiaofeng Zheng and Hongzhong Jin

African ancestry is associated with cluster-based childhood asthma subphenotypes

Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. ...

Authors: Lili Ding, Dan Li, Michael Wathen, Mekibib Altaye and Tesfaye B. Mersha

Burden of de novo mutations and inherited rare single nucleotide variants in children with sensory processing dysfunction

In children with sensory processing dysfunction (SPD), who do not meet criteria for autism spectrum disorder (ASD) or intellectual disability, the contribution of de novo pathogenic mutation in neurodevelopmen...

Authors: Elysa Jill Marco, Anne Brandes Aitken, Vishnu Prakas Nair, Gilberto da Gente, Molly Rae Gerdes, Leyla Bologlu, Sean Thomas and Elliott H. Sherr

Chromosomal microarray analysis in developmental delay and intellectual disability with comorbid conditions

Developmental delay (DD) and intellectual disability (ID) are frequently associated with a broad spectrum of additional phenotypes. Chromosomal microarray analysis (CMA) has been recommended as a first-tier te...

Authors: Yanjie Fan, Yanming Wu, Lili Wang, Yu Wang, Zhuwen Gong, Wenjuan Qiu, Jingmin Wang, Huiwen Zhang, Xing Ji, Jun Ye, Lianshu Han, Xingming Jin, Yongnian Shen, Fei Li, Bing Xiao, Lili Liang…

Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis

There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheol...

Authors: Kira Groen, Vicki E. Maltby, Rodney A. Lea, Katherine A. Sanders, J. Lynn Fink, Rodney J. Scott, Lotti Tajouri and Jeannette Lechner-Scott

Genome-wide association study identifies two loci influencing plasma neurofilament light levels

Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide associati...

Authors: Jie-Qiong Li, Xiang-Zhen Yuan, Hai-Yan Li, Xi-Peng Cao, Jin-Tai Yu, Lan Tan and Wei-An Chen

Integrative analyses of genes and microRNA expressions in human trisomy 21 placentas

The most frequent chromosomal aneuploidy is trisomy 21 (T21) that is caused by an extra copy of chromosome 21. The imbalance of whole genome including genes and microRNAs contributes to the various phenotypes ...

Authors: Ji Hyae Lim, You Jung Han, Hyun Jin Kim, Moon Young Kim, So Yeon Park, Youl-Hee Cho and Hyun Mee Ryu

Clinical providers’ experiences with returning results from genomic sequencing: an interview study

Current medical practice includes the application of genomic sequencing (GS) in clinical and research settings. Despite expanded use of this technology, the process of disclosure of genomic results to patients...

Authors: Julia Wynn, Katie Lewis, Laura M. Amendola, Barbara A. Bernhardt, Sawona Biswas, Manasi Joshi, Carmit McMullen and Sarah Scollon

A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature

Parental balanced reciprocal translocations can result in partial aneuploidies in the offspring due to unbalanced meiotic segregation during gametogenesis. Herein, we report the phenotypic and molecular cytoge...

Authors: C. S. Paththinige, N. D. Sirisena, U. G. I. U. Kariyawasam, R. C. Ediriweera, P. Kruszka, M. Muenke and V. H. W. Dissanayake

DNA methylation in the APOE genomic region is associated with cognitive function in African Americans

Genetic variations in apolipoprotein E (APOE) and proximal genes (PVRL2, TOMM40, and APOC1) are associated with cognitive function and dementia, particularly Alzheimer’s disease. Epigenetic mechanisms such as DNA...

Authors: Jiaxuan Liu, Wei Zhao, Erin B. Ware, Stephen T. Turner, Thomas H. Mosley and Jennifer A. Smith

Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). Nearly 150 pathogenic mutations have been identified in FLCN. The most frequent pattern ...

Authors: Mitsuko Furuya, Hironori Kobayashi, Masaya Baba, Takaaki Ito, Reiko Tanaka and Yukio Nakatani

Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

Decapping of mRNA is an important step in the regulation of mRNA turnover and therefore of gene expression, which is a key process controlling development and homeostasis of all organisms. It has been shown th...

Authors: Ute Scheller, Kathrin Pfisterer, Steffen Uebe, Arif B. Ekici, André Reis, Rami Jamra and Fulvia Ferrazzi