Articles

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

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

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

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

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

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

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

Identifying statistically significant combinatorial markers for survival analysis

Survival analysis methods have been widely applied in different areas of health and medicine, spanning over varying events of interest and target diseases. They can be utilized to provide relationships between...

Authors: Raissa T. Relator, Aika Terada and Jun Sese

Mut2Vec: distributed representation of cancerous mutations

Embedding techniques for converting high-dimensional sparse data into low-dimensional distributed representations have been gaining popularity in various fields of research. In deep learning models, embedding ...

Authors: Sunkyu Kim, Heewon Lee, Keonwoo Kim and Jaewoo Kang

Fuzzy set-based generalized multifactor dimensionality reduction analysis of gene-gene interactions

Gene-gene interactions (GGIs) are a known cause of missing heritability. Multifactor dimensionality reduction (MDR) is one of most commonly used methods for GGI detection. The generalized multifactor dimension...

Authors: Hye-Young Jung, Sangseob Leem and Taesung Park

Population-based statistical inference for temporal sequence of somatic mutations in cancer genomes

It is well recognized that accumulation of somatic mutations in cancer genomes plays a role in carcinogenesis; however, the temporal sequence and evolutionary relationship of somatic mutations remain largely u...

Authors: Je-Keun Rhee and Tae-Min Kim

WISARD: workbench for integrated superfast association studies for related datasets

A Mendelian transmission produces phenotypic and genetic relatedness between family members, giving family-based analytical methods an important role in genetic epidemiological studies—from heritability estima...

Authors: Sungyoung Lee, Sungkyoung Choi, Dandi Qiao, Michael Cho, Edwin K. Silverman, Taesung Park and Sungho Won

EAGLE: Explicit Alternative Genome Likelihood Evaluator

Reliable detection of genome variations, especially insertions and deletions (indels), from single sample DNA sequencing data remains challenging, partially due to the inherent uncertainty involved in aligning...

Authors: Tony Kuo, Martin C. Frith, Jun Sese and Paul Horton

Exact association test for small size sequencing data

Recent statistical methods for next generation sequencing (NGS) data have been successfully applied to identifying rare genetic variants associated with certain diseases. However, most commonly used methods (e...

Authors: Joowon Lee, Seungyeoun Lee, Jin-Young Jang and Taesung Park

LDSplitDB: a database for studies of meiotic recombination hotspots in MHC using human genomic data

Meiotic recombination happens during the process of meiosis when chromosomes inherited from two parents exchange genetic materials to generate chromosomes in the gamete cells. The recombination events tend to ...

Authors: Jing Guo, Hao Chen, Peng Yang, Yew Ti Lee, Min Wu, Teresa M. Przytycka, Chee Keong Kwoh and Jie Zheng

An integrated clinical and genomic information system for cancer precision medicine

Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex natu...

Authors: Yeongjun Jang, Taekjin Choi, Jongho Kim, Jisub Park, Jihae Seo, Sangok Kim, Yeajee Kwon, Seungjae Lee and Sanghyuk Lee

IMPACT web portal: oncology database integrating molecular profiles with actionable therapeutics

With the advancement of next generation sequencing technology, researchers are now able to identify important variants and structural changes in DNA and RNA in cancer patient samples. With this information, we...

Authors: Jennifer D. Hintzsche, Minjae Yoo, Jihye Kim, Carol M. Amato, William A. Robinson and Aik Choon Tan

CAS-viewer: web-based tool for splicing-guided integrative analysis of multi-omics cancer data

The Cancer Genome Atlas (TCGA) project is a public resource that provides transcriptomic, DNA sequence, methylation, and clinical data for 33 cancer types. Transforming the large size and high complexity of TC...

Authors: Seonggyun Han, Dongwook Kim, Youngjun Kim, Kanghoon Choi, Jason E. Miller, Dokyoon Kim and Younghee Lee

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease

Parkinson’s disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD r...

Authors: Lining Su, Chunjie Wang, Chenqing Zheng, Huiping Wei and Xiaoqing Song

Genetic analysis of Wnt/PCP genes in neural tube defects

Mouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical to neural tube clo...

Authors: Zhongzhong Chen, Yunping Lei, Xuanye Cao, Yufang Zheng, Fang Wang, Yihua Bao, Rui Peng, Richard H. Finnell, Ting Zhang and Hongyan Wang

Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report

Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is kno...

Authors: Liuh Ling Goh, Yingshan Lee, Ee Shien Tan, James Soon Chuan Lim, Chia Wei Lim and Rinkoo Dalan

Performance of in silico prediction tools for the classification of rare BRCA1/2 missense variants in clinical diagnostics

The use of next-generation sequencing approaches in clinical diagnostics has led to a tremendous increase in data and a vast number of variants of uncertain significance that require interpretation. Therefore,...

Authors: Corinna Ernst, Eric Hahnen, Christoph Engel, Michael Nothnagel, Jonas Weber, Rita K. Schmutzler and Jan Hauke

HLA and proteasome expression body map

The presentation of HLA peptide complexes to T cells is a highly regulated and tissue specific process involving multiple transcriptionally controlled cellular components. The extensive polymorphism of HLA gen...

Authors: Sebastian Boegel, Martin Löwer, Thomas Bukur, Patrick Sorn, John C. Castle and Ugur Sahin

Integrated analysis of DNA-methylation and gene expression using high-dimensional penalized regression: a cohort study on bone mineral density in postmenopausal women

Using high-dimensional penalized regression we studied genome-wide DNA-methylation in bone biopsies of 80 postmenopausal women in relation to their bone mineral density (BMD). The women showed BMD varying from...

Authors: Tonje G. Lien, Ørnulf Borgan, Sjur Reppe, Kaare Gautvik and Ingrid Kristine Glad

Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Sarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To fi...

Authors: Alain Calender, Pierre Antoine Rollat Farnier, Adrien Buisson, Stéphane Pinson, Abderrazzaq Bentaher, Serge Lebecque, Harriet Corvol, Rola Abou Taam, Véronique Houdouin, Claire Bardel, Pascal Roy, Gilles Devouassoux, Vincent Cottin, Pascal Seve, Jean-François Bernaudin, Clarice X. Lim…

A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy

Electrocardiographic measures of left ventricular hypertrophy (LVH) are used as predictors of cardiovascular risk. We combined linkage and association analyses to discover novel rare genetic variants involved ...

Authors: Claudia Tamar Silva, Irina V. Zorkoltseva, Maartje N. Niemeijer, Marten E. van den Berg, Najaf Amin, Ayşe Demirkan, Elisa van Leeuwen, Adriana I. Iglesias, Laura B. Piñeros-Hernández, Carlos M. Restrepo, Jan A. Kors, Anatoly V. Kirichenko, Rob Willemsen, Ben A. Oostra, Bruno H. Stricker, André G. Uitterlinden…

Impaired type I interferon regulation in the blood transcriptome of recurrent asthma exacerbations

Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased su...

Authors: Jose L. Gomez, Maria P. Diaz, Gustavo Nino and Clemente J. Britto

Whole transcriptome analysis reveals differential gene expression profile reflecting macrophage polarization in response to influenza A H5N1 virus infection

Avian influenza A H5N1 virus can cause lethal disease in humans. The virus can trigger severe pneumonia and lead to acute respiratory distress syndrome. Data from clinical, in vitro and in vivo suggest that vi...

Authors: Na Zhang, Yun-Juan Bao, Amy Hin-Yan Tong, Scott Zuyderduyn, Gary D. Bader, J. S. Malik Peiris, Si Lok and Suki Man-Yan Lee

Cumulative prognostic power of laminin genes in colorectal cancer

Laminins are a major family of extracellular matrix proteins and the main component of basement membranes. Laminins are involved in many if not all stages of cancer progression, and expression of laminin genes...

Authors: Vladimir V. Galatenko, Diana V. Maltseva, Alexey V. Galatenko, Sergey Rodin and Alexander G. Tonevitsky

Circadian succession of molecular processes in living tissues

Oscillations of different origin, period and amplitude play an important role in the regulation of cellular processes. Most widely studied is the circadian or approximately daily variation in gene expression a...

Authors: Abeer Fadda, Mohammed El Anbari and Andrey Ptitsyn

Medical genomics at Belyaev Conference – 2017

Authors: Yuriy L. Orlov, Julio R. Fernandez-Masso, Ming Chen and Ancha V. Baranova

Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel syndrome spectrum disorders

Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagno...

Authors: Andrey V. Marakhonov, Fedor A. Konovalov, Amin Kh. Makaov, Tatyana A. Vasilyeva, Vitaly V. Kadyshev, Varvara A. Galkina, Elena L. Dadali, Sergey I. Kutsev and Rena A. Zinchenko