journal
MENU ▼
Read by QxMD icon Read
search

NPJ Genomic Medicine

journal
https://www.readbyqxmd.com/read/30002876/meta-analysis-of-the-diagnostic-and-clinical-utility-of-genome-and-exome-sequencing-and-chromosomal-microarray-in-children-with-suspected-genetic-diseases
#1
Michelle M Clark, Zornitza Stark, Lauge Farnaes, Tiong Y Tan, Susan M White, David Dimmock, Stephen F Kingsmore
Genetic diseases are leading causes of childhood mortality. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are relatively new methods for diagnosing genetic diseases, whereas chromosomal microarray (CMA) is well established. Here we compared the diagnostic utility (rate of causative, pathogenic, or likely pathogenic genotypes in known disease genes) and clinical utility (proportion in whom medical or surgical management was changed by diagnosis) of WGS, WES, and CMA in children with suspected genetic diseases by systematic review of the literature (January 2011-August 2017) and meta-analysis, following MOOSE/PRISMA guidelines...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29951225/signaling-pathway-screening-platforms-are-an-efficient-approach-to-identify-therapeutic-targets-in-cancers-that-lack-known-driver-mutations-a-case-report-for-a-cancer-of-unknown-primary-origin
#2
Pedro Torres-Ayuso, Sudhakar Sahoo, Garry Ashton, Elvira An, Nicole Simms, Melanie Galvin, Hui Sun Leong, Kristopher K Frese, Kathryn Simpson, Natalie Cook, Andrew Hughes, Crispin J Miller, Richard Marais, Caroline Dive, Matthew G Krebs, John Brognard
Precision medicine aims to tailor cancer therapies to target specific tumor-promoting aberrations. For tumors that lack actionable drivers, which occurs frequently in the clinic, extensive molecular characterization and pre-clinical drug efficacy studies will be required. A cell line maintained at low passage and a patient- derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29928512/identification-of-an-immune-gene-expression-signature-associated-with-favorable-clinical-features-in-treg-enriched-patient-tumor-samples
#3
Kevin B Givechian, Kamil Wnuk, Chad Garner, Stephen Benz, Hermes Garban, Shahrooz Rabizadeh, Kayvan Niazi, Patrick Soon-Shiong
Immune heterogeneity within the tumor microenvironment undoubtedly adds several layers of complexity to our understanding of drug sensitivity and patient prognosis across various cancer types. Within the tumor microenvironment, immunogenicity is a favorable clinical feature in part driven by the antitumor activity of CD8+ T cells. However, tumors often inhibit this antitumor activity by exploiting the suppressive function of regulatory T cells (Tregs), thus suppressing the adaptive immune response. Despite the seemingly intuitive immunosuppressive biology of Tregs, prognostic studies have produced contradictory results regarding the relationship between Treg enrichment and survival...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29760947/incorporating-epilepsy-genetics-into-clinical-practice-a-360%C3%A2-evaluation
#4
Stephanie Oates, Shan Tang, Richard Rosch, Rosalie Lear, Elaine F Hughes, Ruth E Williams, Line H G Larsen, Qin Hao, Hans Atli Dahl, Rikke S Møller, Deb K Pal
We evaluated a new epilepsy genetic diagnostic and counseling service covering a UK population of 3.5 million. We calculated diagnostic yield, estimated clinical impact, and surveyed referring clinicians and families. We costed alternative investigational pathways for neonatal onset epilepsy. Patients with epilepsy of unknown aetiology onset < 2 years; treatment resistant epilepsy; or familial epilepsy were referred for counseling and testing. We developed NGS panels, performing clinical interpretation with a multidisciplinary team...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29736260/mutation-load-estimation-model-as-a-predictor-of-the-response-to-cancer-immunotherapy
#5
Guan-Yi Lyu, Yu-Hsuan Yeh, Yi-Chen Yeh, Yu-Chao Wang
The determination of the mutation load, a total number of nonsynonymous point mutations, by whole-exome sequencing was shown to be useful in predicting the treatment responses to cancer immunotherapy. However, this technique is expensive and time-consuming, which hampers its application in clinical practice. Therefore, the objective of this study was to construct a mutation load estimation model for lung adenocarcinoma, using a small set of genes, as a predictor of the immunotherapy treatment response. Using the somatic mutation data downloaded from The Cancer Genome Atlas (TCGA) database, a computational framework was developed...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29736259/predictors-of-next-generation-sequencing-panel-selection-using-a-shared-decision-making-approach
#6
Eliza Courtney, Shao-Tzu Li, Tarryn Shaw, Yanni Chen, John Carson Allen, Joanne Ngeow
The introduction of next-generation sequencing panels has transformed the approach for genetic testing in cancer patients, however, established guidelines for their use are lacking. A shared decision-making approach has been adopted by our service, where patients play an active role in panel selection and we sought to identify factors associated with panel selection and report testing outcomes. Demographic and clinical data were gathered for female breast and/or ovarian cancer patients aged 21 and over who underwent panel testing...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29644095/rapid-whole-genome-sequencing-decreases-infant-morbidity-and-cost-of-hospitalization
#7
Lauge Farnaes, Amber Hildreth, Nathaly M Sweeney, Michelle M Clark, Shimul Chowdhury, Shareef Nahas, Julie A Cakici, Wendy Benson, Robert H Kaplan, Richard Kronick, Matthew N Bainbridge, Jennifer Friedman, Jeffrey J Gold, Yan Ding, Narayanan Veeraraghavan, David Dimmock, Stephen F Kingsmore
Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands also received standard genetic testing as clinically indicated...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29619247/cardiac-arrhythmia-and-neuroexcitability-gene-variants-in-resected-brain-tissue-from-patients-with-sudden-unexpected-death-in-epilepsy-sudep
#8
Daniel Friedman, Kasthuri Kannan, Arline Faustin, Seema Shroff, Cheddhi Thomas, Adriana Heguy, Jonathan Serrano, Matija Snuderl, Orrin Devinsky
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic-clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29581887/improving-imputation-in-disease-relevant-regions-lessons-from-cystic-fibrosis
#9
Naim Panjwani, Bowei Xiao, Lizhen Xu, Jiafen Gong, Katherine Keenan, Fan Lin, Gengming He, Zeynep Baskurt, Sangook Kim, Lin Zhang, Mohsen Esmaeili, Scott Blackman, Stephen W Scherer, Harriet Corvol, Mitchell Drumm, Michael Knowles, Garry Cutting, Johanna M Rommens, Lei Sun, Lisa J Strug
Does genotype imputation with public reference panels identify variants contributing to disease? Genotype imputation using the 1000 Genomes Project (1KG; 2504 individuals) displayed poor coverage at the causal cystic fibrosis (CF) transmembrane conductance regulator ( CFTR ) locus for the International CF Gene Modifier Consortium. Imputation with the larger Haplotype Reference Consortium (HRC; 32,470 individuals) displayed improved coverage but low sensitivity of variants clinically relevant for CF. A hybrid reference that combined whole genome sequencing (WGS) from 101 CF individuals with the 1KG imputed a greater number of single-nucleotide variants (SNVs) that would be analyzed in a genetic association study ( r 2  ≥ 0...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29479477/clinical-testing-of-brca1-and-brca2-a-worldwide-snapshot-of-technological-practices
#10
Amanda Ewart Toland, Andrea Forman, Fergus J Couch, Julie O Culver, Diana M Eccles, William D Foulkes, Frans B L Hogervorst, Claude Houdayer, Ephrat Levy-Lahad, Alvaro N Monteiro, Susan L Neuhausen, Sharon E Plon, Shyam K Sharan, Amanda B Spurdle, Csilla Szabo, Lawrence C Brody
Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1 / BRCA2 ...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29449963/the-nsight1-randomized-controlled-trial-rapid-whole-genome-sequencing-for-accelerated-etiologic-diagnosis-in-critically-ill-infants
#11
Josh E Petrikin, Julie A Cakici, Michelle M Clark, Laurel K Willig, Nathaly M Sweeney, Emily G Farrow, Carol J Saunders, Isabelle Thiffault, Neil A Miller, Lee Zellmer, Suzanne M Herd, Anne M Holmes, Serge Batalov, Narayanan Veeraraghavan, Laurie D Smith, David P Dimmock, J Steven Leeder, Stephen F Kingsmore
Genetic disorders are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing is useful for genetic disease diagnosis, results are usually reported too late to guide inpatient management. We performed an investigator-initiated, partially blinded, pragmatic, randomized, controlled trial to test the hypothesis that rapid whole-genome sequencing (rWGS) increased the proportion of NICU/PICU infants receiving a genetic diagnosis within 28 days...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29423277/a-phenotype-centric-benchmark-of-variant-prioritisation-tools
#12
Denise Anderson, Timo Lassmann
Next generation sequencing is a standard tool used in clinical diagnostics. In Mendelian diseases the challenge is to discover the single etiological variant among thousands of benign or functionally unrelated variants. After calling variants from aligned sequencing reads, variant prioritisation tools are used to examine the conservation or potential functional consequences of variants. We hypothesised that the performance of variant prioritisation tools may vary by disease phenotype. To test this we created benchmark data sets for variants associated with different disease phenotypes...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29387454/whole-genome-transcriptomic-insights-into-protective-molecular-mechanisms-in-metabolically-healthy-obese-african-americans
#13
Amadou Gaye, Ayo P Doumatey, Sharon K Davis, Charles N Rotimi, Gary H Gibbons
Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO)...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29367880/cytogenomic-identification-and-long-read-single-molecule-real-time-smrt-sequencing-of-a-bardet-biedl-syndrome-9-bbs9-deletion
#14
Jennifer Reiner, Laura Pisani, Wanqiong Qiao, Ram Singh, Yao Yang, Lisong Shi, Wahab A Khan, Robert Sebra, Ninette Cohen, Arvind Babu, Lisa Edelmann, Ethylin Wang Jabs, Stuart A Scott
Bardet-Biedl syndrome (BBS) is a recessive disorder characterized by heterogeneous clinical manifestations, including truncal obesity, rod-cone dystrophy, renal anomalies, postaxial polydactyly, and variable developmental delays. At least 20 genes have been implicated in BBS, and all are involved in primary cilia function. We report a 1-year-old male child from Guyana with obesity, postaxial polydactyly on his right foot, hypotonia, ophthalmologic abnormalities, and developmental delay, which together indicated a clinical diagnosis of BBS...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29354287/a-robust-targeted-sequencing-approach-for-low-input-and-variable-quality-dna-from-clinical-samples
#15
Austin P So, Anna Vilborg, Yosr Bouhlal, Ryan T Koehler, Susan M Grimes, Yannick Pouliot, Daniel Mendoza, Janet Ziegle, Jason Stein, Federico Goodsaid, Michael Y Lucero, Francisco M De La Vega, Hanlee P Ji
Next-generation deep sequencing of gene panels is being adopted as a diagnostic test to identify actionable mutations in cancer patient samples. However, clinical samples, such as formalin-fixed, paraffin-embedded specimens, frequently provide low quantities of degraded, poor quality DNA. To overcome these issues, many sequencing assays rely on extensive PCR amplification leading to an accumulation of bias and artifacts. Thus, there is a need for a targeted sequencing assay that performs well with DNA of low quality and quantity without relying on extensive PCR amplification...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29354286/pan-cancer-screen-for-mutations-in-non-coding-elements-with-conservation-and-cancer-specificity-reveals-correlations-with-expression-and-survival
#16
Henrik Hornshøj, Morten Muhlig Nielsen, Nicholas A Sinnott-Armstrong, Michał P Świtnicki, Malene Juul, Tobias Madsen, Richard Sallari, Manolis Kellis, Torben Ørntoft, Asger Hobolth, Jakob Skou Pedersen
Cancer develops by accumulation of somatic driver mutations, which impact cellular function. Mutations in non-coding regulatory regions can now be studied genome-wide and further characterized by correlation with gene expression and clinical outcome to identify driver candidates. Using a new two-stage procedure, called ncDriver, we first screened 507 ICGC whole-genomes from 10 cancer types for non-coding elements, in which mutations are both recurrent and have elevated conservation or cancer specificity. This identified 160 significant non-coding elements, including the TERT promoter, a well-known non-coding driver element, as well as elements associated with known cancer genes and regulatory genes (e...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29075515/characterisation-of-the-changing-genomic-landscape-of-metastatic-melanoma-using-cell-free-dna
#17
Anthony Cutts, Oliver Venn, Alexander Dilthey, Avinash Gupta, Dimitris Vavoulis, Helene Dreau, Mark Middleton, Gil McVean, Jenny C Taylor, Anna Schuh
Cancer is characterised by complex somatically acquired genetic aberrations that manifest as intra-tumour and inter-tumour genetic heterogeneity and can lead to treatment resistance. In this case study, we characterise the genome-wide somatic mutation dynamics in a metastatic melanoma patient during therapy using low-input (50 ng) PCR-free whole genome sequencing of cell-free DNA from pre-treatment and post-relapse blood samples. We identify de novo tumour-specific somatic mutations from cell-free DNA, while the sequence context of single nucleotide variants showed the characteristic UV-damage mutation signature of melanoma...
September 4, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28690869/the-clinical-impact-of-copy-number-variants-in-inherited-bone-marrow-failure-syndromes
#18
Nicolas Waespe, Santhosh Dhanraj, Manju Wahala, Elena Tsangaris, Tom Enbar, Bozana Zlateska, Hongbing Li, Robert J Klaassen, Conrad V Fernandez, Geoff D E Cuvelier, John K Wu, Yves D Pastore, Mariana Silva, Jeffrey H Lipton, Joseé Brossard, Bruno Michon, Sharon Abish, MacGregor Steele, Roona Sinha, Mark J Belletrutti, Vicky R Breakey, Lawrence Jardine, Lisa Goodyear, Liat Kofler, Michaela Cada, Lillian Sung, Mary Shago, Stephen W Scherer, Yigal Dror
Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs) were compared to cases with other mutations...
May 10, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28649445/variable-phenotype-expression-in-a-family-segregating-microdeletions-of-the-nrxn1-and-mbd5-autism-spectrum-disorder-susceptibility-genes
#19
Marc Woodbury-Smith, Rob Nicolson, Mehdi Zarrei, Ryan K C Yuen, Susan Walker, Jennifer Howe, Mohammed Uddin, Ny Hoang, Janet A Buchanan, Christina Chrysler, Ann Thompson, Peter Szatmari, Stephen W Scherer
Autism Spectrum Disorder (ASD) is a developmental condition of early childhood onset, which impacts socio-communicative functioning and is principally genetic in etiology. Currently, more than 50 genomic loci are deemed to be associated with susceptibility to ASD, showing de novo and inherited unbalanced copy number variants (CNVs) and smaller insertions and deletions (indels), more complex structural variants (SVs), as well as single nucleotide variants (SNVs) deemed of pathological significance. However, the phenotypes associated with many of these genes are variable, and penetrance is largely unelaborated in clinical descriptions...
May 3, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28649446/phenotypic-profiling-of-cftr-modulators-in-patient-derived-respiratory-epithelia
#20
Saumel Ahmadi, Zoltan Bozoky, Michelle Di Paola, Sunny Xia, Canhui Li, Amy P Wong, Leigh Wellhauser, Steven V Molinski, Wan Ip, Hong Ouyang, Julie Avolio, Julie D Forman-Kay, Felix Ratjen, Jeremy A Hirota, Johanna Rommens, Janet Rossant, Tanja Gonska, Theo J Moraes, Christine E Bear
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations...
April 14, 2017: NPJ Genomic Medicine
journal
journal
53414
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"