• Genomics & Informatics
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• v.17 no.2
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• pp.15.1-15.7
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• 2019

Automatically detecting mentions of pharmaceutical drugs and chemical substances is key for the subsequent extraction of relations of chemicals with other biomedical entities such as genes, proteins, diseases, adverse reactions or symptoms. The identification of drug mentions is also a prior step for complex event types such as drug dosage recognition, duration of medical treatments or drug repurposing. Formally, this task is known as named entity recognition (NER), meaning automatically identifying mentions of predefined entities of interest in running text. In the domain of medical texts, for chemical entity recognition (CER), techniques based on hand-crafted rules and graph-based models can provide adequate performance. In the recent years, the field of natural language processing has mainly pivoted to deep learning and state-of-the-art results for most tasks involving natural language are usually obtained with artificial neural networks. Competitive resources for drug name recognition in English medical texts are already available and heavily used, while for other languages such as Spanish these tools, although clearly needed were missing. In this work, we adapt an existing neural NER system, NeuroNER, to the particular domain of Spanish clinical case texts, and extend the neural network to be able to take into account additional features apart from the plain text. NeuroNER can be considered a competitive baseline system for Spanish drug and CER promoted by the Spanish national plan for the advancement of language technologies (Plan TL).

• Genomics & Informatics
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• v.16 no.4
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• pp.22.1-22.5
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• 2018

In 1966, the International Classification of Viruses (ICNV) was established to standardize the naming of viruses. In 1975, the organization was renamed "International Committee on Taxonomy of Viruses (ICTV)," by which it is still known today. The primary virus classification provided by ICTV in 1971 was for viruses infecting vertebrates, which includes 19 genera, 2 families, and 24 unclassified groups. Presently, the 10th virus taxonomy has been published. However, the early classification of viruses was based on clinical results "in vivo" and "in vitro," as well as on the shape of the Phenotype virus. Due to the development of next-generation sequencing and the accompanying bioinformatics analysis pipelines, a reconstruction of the classification system has been proposed. At a meeting held in Boston, USA between June 9-11, 2016, there was even an in-depth discussion regarding the classification of viruses using metagenomic data. One suggested activity that arose from the meeting was that viral taxonomy should be reconstructed, based on genotype and bioinformatics analysis "in silico." This article describes our efforts to achieve this goal by construction of a web-based system and the extension of an associated database, based on ICTV taxonomy. This virus taxonomy web system was designed specifically to extend the virus taxonomy up to strain and isolation, which was then connected with the NCBI database to facilitate searches for specific viral genes; there are also links to journals provided by the EMBL RESTful API that improves accessibility for academic groups.

• Genomics & Informatics
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• v.16 no.4
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• pp.23.1-23.5
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• 2018

Virus taxonomy was initially determined by clinical experiments based on phenotype. However, with the development of sequence analysis methods, genotype-based classification was also applied. With the development of genome sequence analysis technology, there is an increasing demand for virus taxonomy to be extended from in vivo and in vitro to in silico. In this study, we verified the consistency of the current International Committee on Taxonomy of Viruses taxonomy using an in silico approach, aiming to identify the specific sequence for each virus. We applied this approach to norovirus in Caliciviridae, which causes 90% of gastroenteritis cases worldwide. First, based on the dogma "protein structure determines its function," we hypothesized that the specific sequence can be identified by the specific structure. Firstly, we extracted the coding region (CDS). Secondly, the CDS protein sequences of each genus were annotated by the conserved domain database (CDD) search. Finally, the conserved domains of each genus in Caliciviridae are classified by RPS-BLAST with CDD. The analysis result is that Caliciviridae has sequences including RNA helicase in common. In case of Norovirus, Calicivirus coat protein C terminal and viral polyprotein N-terminal appears as a specific domain in Caliciviridae. It does not include in the other genera in Caliciviridae. If this method is utilized to detect specific conserved domains, it can be used as classification keywords based on protein functional structure. After determining the specific protein domains, the specific protein domain sequences would be converted to gene sequences. This sequences would be re-used one of viral bio-marks.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.31-38
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• 2019

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder of which m.3243A>G is the most commonly associated mutation, resulting in an inability to meet the energy requirements of various organs. MELAS poses a diagnostic challenge owing to its multiple organ involvement and great clinical variability due to its heteroplasmic nature. We report three cases from a family who were initially misdiagnosed with myasthenia gravis or undiagnosed. Although there is no optimal consensus treatment approach for patients with MELAS because of the disease's heterogeneity, our 21-year-long therapy regimen of ${\text\tiny{L}}-arginine$, ${\text\tiny{L}}-carnitine$, and coenzyme Q10 supplementation combined with dietary management appeared to provide noticeable protection from the symptoms and complications. Prompt early diagnosis is important, as optimal multidisciplinary management and early intervention may improve outcomes.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.79-82
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• 2020

In epilepsy-aphasia spectrum (EAS) disorders, mutations in the glutamate receptor ionotropic N-methyl-D-aspartate type subunit 2A (GRIN2A) have become important for screening the disease. Research into the phenotypic variability of several types of neurologic impairment involving these mutations is in progress. However, the non-neurological problems related to these mutations are poorly understood. EAS disorders usually have epileptic, cognitive, or behavioral manifestations. In this case report, we present a female patient with epilepsy, delay in expressive language and social development, and intellectual disability with low intelligence quotient and memory quotient, but normal motor development. Through genetic analysis, she was found to have a missense and a nonsense mutation in GRIN2A (c.1770A>C; p.Lys509Asn and c.3187G>T; p.Glu1063∗, respectively) and we consider the nonsense mutation as 'pathogenic variant'. She was also discovered to have congenital hypothyroidism, growth hormone deficiency and Rathke's cleft cyst in the brain, which were previously unknown features of GRIN2A mutation. Our findings should widen understanding of the spectrum of GRIN2A phenotypes, and emphasize the need for more research into the association between GRIN2A mutations and non-neurologic clinical presentations.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.102-107
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• 2020

We report the case of an infant with a 4q35.1 deletion with 10p duplication. This mutation is rarely reported in the literature and has been found to have variable clinical findings, often including developmental delay. In this case, the condition was detected by chromosomal microarray analysis after initial manifestation of a feeding problem and developmental delay. Minor dysmorphic features with abnormal neurological examination led to further evaluation. The father's chromosome complement was 46, XY, t(4;10)(q35;p12.2). Parental balanced translocation can go unrecognized, because affected individuals are often phenotypically healthy until they have fertility issues such as recurrent miscarriages or children with severe congenital disorders. Genetic diagnoses help to establish a clear family genetic background that permits the development of clear treatment strategies. Prenatal counseling can also help to understand the possible risks associated with pregnancy or future child planning.

• Journal of Interdisciplinary Genomics
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• v.4 no.1
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• pp.7-10
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• 2022

Purpose:Maturity onset diabetes of the young (MODY) is the most common hereditary form of diabetes mellitus (DM), with similar clinical manifestations to type 1 or type 2 DM, leading to diagnostic ambiguity. Despite increased genetic research on monogenic DM, studies with Asian populations are limited. Therefore, we investigated mutation in possible monogenic DM and MODY in Korean children and aldolescents. Methods: Targeted panel exome sequencing including 32 targets genes was performed for 41 patients with suspected monogenic DM at Kyungpook National University Children's Hospital. Results: Variants were detected in 19 patients, including those in known MODY-associated genes (HNF4A, GCK, HNF1A, CEL, PAX4, INS, and BLK) and monogenic DM-associated genes (WFS1, FRX6, and GLIS3). Conclusion: MODY variants were detected more than expected. Targeted exon sequencing is helpful in diagnosing MODY or possible monogenic DM patients.

• Journal of Interdisciplinary Genomics
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• v.4 no.1
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• pp.15-18
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• 2022

Hemophilia A is a rare X-linked congenital deficiency of clotting factor VIII (FVIII) that is traditionally diagnosed by measuring FVIII activity. Various mutations of the FVIII gene have been reported and they influence on the FVIII protein structure. A deficiency of or reduction in FVIII protein manifests as spontaneous or induced bleeding depending on the disease severity. Mutations of the FVIII gene provide important information on the severity of disease and inhibitor development. FVIII mutations also affect the discrepant activities found using different FVIII assays. FVIII activity is affected differently depending on the mutation site. Long-range PCR is commonly used to detect intron 22 inversion, the most common mutation in severe hemophilia. However, point mutations are also common in patients with hemophilia, and direct Sanger sequencing and copy number variant analysis are being used to screen for full mutations in the FVIII gene. Advances in molecular genetic methods, such as next-generation sequencing, may enable accurate analysis of mutations in the factor VIII gene, which may be useful in the diagnosis of mild to moderate hemophilia. Genetic analysis is also useful in diagnosing carriers and managing bleeding control. This review discusses the current knowledge about mutations in hemophilia and focuses on the clinical aspects associated with these mutations and the importance of genetic analysis.

• Genomics & Informatics
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• v.20 no.1
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• pp.7.1-7.13
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• 2022

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

• Genomics & Informatics
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• v.19 no.4
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• pp.41.1-41.10
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• 2021

In addition to mutations and copy number alterations, gene fusions are commonly identified in cancers. In thyroid cancer, fusions of important cancer-related genes have been commonly reported; however, extant panels do not cover all clinically important gene fusions. In this study, we aimed to develop a custom RNA-based sequencing panel to identify the key fusions in thyroid cancer. Our ThyChase panel was designed to detect 87 types of gene fusion. As quality control of RNA sequencing, five housekeeping genes were included in this panel. When we applied this panel for the analysis of fusions containing reference RNA (HD796), three expected fusions (EML4-ALK, CCDC6-RET, and TPM3-NTRK1) were successfully identified. We confirmed the fusion breakpoint sequences of the three fusions from HD796 by Sanger sequencing. Regarding the limit of detection, this panel could detect the target fusions from a tumor sample containing a 1% fusion-positive tumor cellular fraction. Taken together, our ThyChase panel would be useful to identify gene fusions in the clinical field.