scholarly journals Targeted resequencing for large-scale genomic studies: accelerating NGS throughput using molecular barcodes

2010 ◽  
Vol 7 (6) ◽  
pp. i-ii ◽  
Author(s):  
Julia Lange
Keyword(s):  
Large Scale ◽  
Targeted Resequencing ◽  
Genomic Studies ◽  
Molecular Barcodes

scholarly journals Gene Expression Imputation with Generative Adversarial Imputation Nets

2020 ◽  
Author(s):  
Ramon Viñas ◽  
Tiago Azevedo ◽  
Eric R. Gamazon ◽  
Pietro Liò
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Biological Significance ◽  
Predictive Performance ◽  
Cost Effective ◽  
Rna Seq ◽  
Comprehensive Collection ◽  
Genomic Studies ◽  
Biological Discovery ◽  
Cancer Types

AbstractA question of fundamental biological significance is to what extent the expression of a subset of genes can be used to recover the full transcriptome, with important implications for biological discovery and clinical application. To address this challenge, we present GAIN-GTEx, a method for gene expression imputation based on Generative Adversarial Imputation Networks. In order to increase the applicability of our approach, we leverage data from GTEx v8, a reference resource that has generated a comprehensive collection of transcriptomes from a diverse set of human tissues. We compare our model to several standard and state-of-the-art imputation methods and show that GAIN-GTEx is significantly superior in terms of predictive performance and runtime. Furthermore, our results indicate strong generalisation on RNA-Seq data from 3 cancer types across varying levels of missingness. Our work can facilitate a cost-effective integration of large-scale RNA biorepositories into genomic studies of disease, with high applicability across diverse tissue types.

Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency

2017 ◽  
Vol 88 (6) ◽  
pp. 408-417 ◽  
Author(s):  
Greta Grosse ◽  
Alina Hilger ◽  
Michael Ludwig ◽  
Heiko Reutter ◽  
Franziska Lorenzen ◽  
...  
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Targeted Resequencing ◽  
Targeted Next Generation Sequencing ◽  
Increased Risk ◽  
Igf I ◽  
Novel Variant ◽  
Unaffected Parent ◽  
Next Generation Sequencing Ngs ◽  
Clinical Phenotyping

Background/Aims: To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)-based resequencing of growth-related genes. Methods: Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. Results: We identified disease-causing, heterozygous, de novo variants in HRAS (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous GHR nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in SH2B1 and SOCS2, both were inherited from an unaffected parent. Conclusions: Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations.

scholarly journals East Asian-specific novel loci associated with late-onset Alzheimer’s disease: the GARD cohort Genome-wide study

2020 ◽  
Author(s):  
Sarang Kang ◽  
Tamil Iniyan Gunasekaran ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
Sungho Won ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Genetic Factors ◽  
Late Onset ◽  
East Asian ◽  
Genetic Heritability ◽  
Genome Wide ◽  
Japanese Sample ◽  
Genomic Studies

ABSTRACTThe high genetic heritability of Alzheimer’s disease has contributed to the multi-directional and large-scale genomic studies to discover genetic factors, and so far many massive studies have been reported. However, the majority of genetic factors have been identified through European races, and relatively few studies using East Asians to discover genetic factors. In this study, East Asian specific loci is first reported through GWAS using GARD cohorts, which have been intensively recruited and managed by a single institution. ApoE-stratified GWAS with the AD cases and matched controls (n=2,291) in the Korean cohort and validation analysis using a Japanese sample (n=1,956) replicated six previously reported loci (genes) including ApoE and suggested two novel susceptible loci in LRIG1 and CACNA1A gene. This study demonstrates that discovery of AD-associated variants can be accomplished in ethnic groups of a more homogeneous genetic background using samples comprising fewer subjects.

scholarly journals Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection

2016 ◽  
Author(s):  
Antonio F Pardiñas ◽  
Peter Holmans ◽  
Andrew J Pocklington ◽  
Valentina Escott-Price ◽  
Stephan Ripke ◽  
...  
Keyword(s):  
Large Scale ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Meta Analysis ◽  
Single Gene ◽  
Poor Quality ◽  
Background Selection ◽  
Loss Of Function ◽  
Risk Variants ◽  
Genomic Studies

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide such insight. We report the largest single cohort genome-wide association study of schizophrenia (11,260 cases and 24,542 controls) and through meta-analysis with existing data we identify 50 novel GWAS loci. Using gene-wide association statistics we implicate an additional set of 22 novel associations that map onto a single gene. We show for the first time that the common variant association signal is highly enriched among genes that are intolerant to loss of function mutations and that variants in these genes persist in the population despite the low fecundity associated with the disorder through the process of background selection. Associations point to novel areas of biology (e.g. metabotropic GABA-B signalling and acetyl cholinesterase), reinforce those implicated in earlier GWAS studies (e.g. calcium channel function), converge with earlier rare variants studies (e.g. NRXN1, GABAergic signalling), identify novel overlaps with autism (e.g. RBFOX1, FOXP1, FOXG1), and support early controversial candidate gene hypotheses (e.g. ERBB4 implicating neuregulin signalling). We also demonstrate the involvement of six independent central nervous system functional gene sets in schizophrenia pathophysiology. These findings provide novel insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation intolerant genes and suggest a mechanism by which common risk variants are maintained in the population.

scholarly journals Precision cancer therapy by molecular profiling – A Theoretical Study

2021 ◽  
Author(s):  
V. Sah
Keyword(s):  
Large Scale ◽  
Clinical Decision Making ◽  
Single Cell Analysis ◽  
Clinical Decision ◽  
Molecular Profiling ◽  
Outcome Analysis ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Next Generation Sequencing Technology ◽  
Genomic Studies

The amount of druggable tumor-specific molecular aberrations has increased significantly over the last decade, with biomarker-matched therapies demonstrating a major survival advantage in many cancer forms. Therefore, molecular pathology has been critical not just for tumor detection and prognosis, but also for clinical decision-making in everyday practice. The advent of next-generation sequencing technology and the proliferation of large-scale tumor molecular profiling services through universities worldwide have transformed the area of precision oncology. When systematic genomic studies become more accessible in clinical and laboratory environments, healthcare professionals face the difficult challenge of outcome analysis and translation. This study summarizes existing and future methods to implementing precision cancer medicine, outlining the obstacles and possible strategies for facilitating the understanding and maximization of molecular profiling findings. Beyond tumor DNA sequencing, we discuss innovative molecular characterization techniques such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analysis. Additionally, we discuss present and future uses of liquid biopsies for evaluating blood-based biomarkers such as circulating tumor cells and nucleic acids. Finally, the shortcomings of genotype-based treatments give insight into opportunities to extend personalized medicine beyond genomics.

scholarly journals Genetics of Prostate Carcinoma

2021 ◽  
Vol 50 (1) ◽  
pp. 71
Author(s):  
Božo Krušlin ◽  
Lucija Škara ◽  
Tonći Vodopić ◽  
Borna Vrhovec ◽  
Jure Murgić ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Carcinoma ◽  
Poor Prognosis ◽  
Large Scale ◽  
Metastatic Prostate Cancer ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Genomic Studies ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

<p>The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of prostate cancer. Another urgent need is developing highly metastatic prostate cancer models, as only up to 17% of available models dis- play bone metastases and exhibit a less typical neuroendocrine prostate cancer or sarcomatoid carcinoma. Moreover, androgen deprivation and relapse should be mimicked in the genetically engineered mouse models, as androgen independence may yield a better model for metastatic castrate-resistant prostate cancer. The development of such refined animal models should be guid- ed by comparative genomics of primary versus corresponding metastatic tumors. Such an approach will have the potential to illuminate the key genetic events associated with specific molecular prostate cancer subsets and indicate directions for effective therapy.</p><p><strong>Conclusion</strong>. Despite excellent results in the treatment of localized prostatic carcinoma, castrate-resistant prostate can- cer and metastatic prostate cancer have a poor prognosis. Advanced large-scale genomic studies revealed a large number of ge- netic alterations in PCa. Experimental models of prostate carcinoma in genetically modified mice could provide new data about the genetic changes in such cancers and help in developing better animal models for treatment resistant prostate carcinomas.</p>

scholarly journals Phylogeographic separation and formation of sexually discrete lineages in a global population of Yersinia pseudotuberculosis

2017 ◽  
Author(s):  
Tristan Seecharran ◽  
Laura Kalin-Mänttäri ◽  
Katja A. Koskela ◽  
Simo Nikkari ◽  
Benjamin Dickins ◽  
...  
Keyword(s):  
Large Scale ◽  
Yersinia Pseudotuberculosis ◽  
Genomic Analysis ◽  
Genetic Exchange ◽  
Evolutionary Trajectory ◽  
Population Genomic ◽  
The World ◽  
Genomic Studies ◽  
Lineage Structure ◽  
Global Population

AbstractYersinia pseudotuberculosis is a Gram negative intestinal pathogen of humans and has been responsible for several nation-wide gastro-intestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic Yersinia, Y. pestis and Y. enterocolitica allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no large-scale global population genomic analysis of Y. pseudotuberculosis has been performed. Here we present analyses of the genomes of 134 strains of Y. pseudotuberculosis isolated from around the world, from multiple ecosystems since 1960’s. Our data display a phylogeographic split within the population, with an Asian ancestry and subsequent dispersal of successful clonal lineages into Europe and the rest of the world. These lineages can be differentiated by CRISPR cluster arrays, and we show that the lineages are limited with respect to inter-lineage genetic exchange. This restriction of genetic exchange maintains the discrete lineage structure in the population despite co-existence of lineages for thousands of years in multiple countries. Our data highlights how CRISPR can be informative of the evolutionary trajectory of bacterial lineages, and merits further study across bacteria.

scholarly journals Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels

2010 ◽  
Vol 19 (9) ◽  
pp. 1863-1872 ◽  
Author(s):  
M. Barbalic ◽  
J. Dupuis ◽  
A. Dehghan ◽  
J. C. Bis ◽  
R. C. Hoogeveen ◽  
...  
Keyword(s):  
Large Scale ◽  
Genomic Studies

Neurobiology of Trauma and Stressor-Related Disorders

2018 ◽  
Author(s):  
Marissa Elizabeth Maheu ◽  
Joseph Hunter Howie ◽  
Kerry James Ressler
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Stress Response ◽  
Posttraumatic Stress ◽  
Large Scale ◽  
Stress Disorder ◽  
Acute Stress ◽  
Molecular Techniques ◽  
Fear Learning ◽  
Recent Developments ◽  
Genomic Studies

Posttraumatic stress disorder (PTSD) and acute stress disorder are precipitated by exposure to one or more traumatic events, and result in debilitating fear-related symptoms. Advances made over the past several years have greatly improved our understanding of these disorders, as well as the neurobiological and genetic factors that contribute to their emergence and progression. In this review, we provide an overview of this research, with a particular focus on recent developments in understanding the neurocircuitry underlying relevant aspects of fear learning, including acquisition, generalization, and the extinction of fear. Molecular regulators of stress response and candidate genes implicated in PTSD are also discussed. Although there remains a great deal to learn about these disorders, novel approaches, large-scale genomic studies, and new molecular techniques promise to help untangle the neurobiology of trauma- and stressor-related illness over the coming years. This review contains 3 figures, 3 tables and 56 references Key words: Posttraumatic stress disorder, fear, genetics, GWAS, HPA stress response, neurocircuitry models of trauma, generalization, extinction learning.

scholarly journals Unified methods for feature selection in large-scale genomic studies with censored survival outcomes

2020 ◽  
Vol 36 (11) ◽  
pp. 3409-3417
Author(s):  
Lauren Spirko-Burns ◽  
Karthik Devarajan
Keyword(s):  
Feature Selection ◽  
Large Scale ◽  
Proportional Hazards ◽  
Cox Model ◽  
Supplementary Information ◽  
Genomic Feature ◽  
Prognostic Impact ◽  
Genomic Features ◽  
Special Cases ◽  
Genomic Studies

Abstract Motivation One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous datasets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards (PH), which is unlikely to hold for each feature. When applied to genomic features exhibiting some form of non-proportional hazards (NPH), these methods could lead to an under- or over-estimation of the effects. We propose a broad array of marginal screening techniques that aid in feature ranking and selection by accommodating various forms of NPH. First, we develop an approach based on Kullback–Leibler information divergence and the Yang–Prentice model that includes methods for the PH and proportional odds (PO) models as special cases. Next, we propose R2 measures for the PH and PO models that can be interpreted in terms of explained randomness. Lastly, we propose a generalized pseudo-R2 index that includes PH, PO, crossing hazards and crossing odds models as special cases and can be interpreted as the percentage of separability between subjects experiencing the event and not experiencing the event according to feature measurements. Results We evaluate the performance of our measures using extensive simulation studies and publicly available datasets in cancer genomics. We demonstrate that the proposed methods successfully address the issue of NPH in genomic feature selection and outperform existing methods. Availability and implementation R code for the proposed methods is available at github.com/lburns27/Feature-Selection. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

Sign in / Sign up

Export Citation Format

Share Document