Exploring the impact and utility of genomic sequencing in established CKD
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PROVIDER: S-EPMC10921391 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Background and objectivesGenomic sequencing (GS) is increasingly used for diagnostic evaluation, yet follow-up care is not well understood. We assessed clinicians' recommendations after GS, parent-reported follow-up, and actions parents initiated in response to learning their child's GS results.MethodsWe surveyed parents of children who received GS through the Clinical Sequencing Evidence Generating Research consortium ∼5 to 7 months after return of results. We compared the proportion of parents who reported discussing their child's result with a clinician, clinicians' recommendations, and parents' follow-up actions by GS result type using χ2 tests.ResultsA total of 1188 respondents completed survey measures on recommended medical actions (n = 1187) and/or parent-initiated actions (n = 913). Most parents who completed recommended medical actions questions (n = 833, 70.3%) reported having discussed their child's GS results with clinicians. Clinicians made recommendations to change current care for patients with positive GS results (n = 79, 39.1%) more frequently than for those with inconclusive (n = 31, 12.4%) or negative results (n = 44, 11.9%; P < .001). Many parents discussed (n = 152 completed, n = 135 planned) implications of GS results for future pregnancies with a clinician. Aside from clinical recommendations, 13.0% (n = 119) of parents initiated changes to their child's health or lifestyle.ConclusionsIn diverse pediatric clinical contexts, GS results can lead to recommendations for follow-up care, but they likely do not prompt large increases in the quantity of care received.
| S-EPMC10812387 | biostudies-literature
Project description:Whole-genome sequencing (WGS) is positioned to become one of the most robust strategies for achieving timely diagnosis of rare genomic diseases. Despite its favorable diagnostic performance compared to conventional testing strategies, routine use and reimbursement of WGS are hampered by inconsistencies in the definition and measurement of clinical utility. For example, what constitutes clinical utility for WGS varies by stakeholder's perspective (physicians, patients, families, insurance companies, health-care organizations, and society), clinical context (prenatal, pediatric, critical care, adult medicine), and test purpose (diagnosis, screening, treatment selection). A rapidly evolving technology landscape and challenges associated with robust comparative study design in the context of rare disease further impede progress in this area of empiric research. To address this challenge, an expert working group of the Medical Genome Initiative was formed. Following a consensus-based process, we align with a broad definition of clinical utility and propose a conceptually-grounded and empirically-guided measurement toolkit focused on four domains of utility: diagnostic thinking efficacy, therapeutic efficacy, patient outcome efficacy, and societal efficacy. For each domain of utility, we offer specific indicators and measurement strategies. While we focus on diagnostic applications of WGS for rare germline diseases, this toolkit offers a flexible framework for best practices around measuring clinical utility for a range of WGS applications. While we expect this toolkit to evolve over time, it provides a resource for laboratories, clinicians, and researchers looking to characterize the value of WGS beyond the laboratory.
| S-EPMC7738524 | biostudies-literature
Project description:BackgroundRestriction site-Associated DNA sequencing (RAD-Seq) is widely applied to generate genome-wide sequence and genetic marker datasets. RAD-Seq has been extensively utilised, both at the population level and across species, for example in the construction of phylogenetic trees. However, the consistency of RAD-Seq data generated in different laboratories, and the potential use of cross-species orthologous RAD loci in the estimation of genetic relationships, have not been widely investigated. This study describes the use of SbfI RAD-Seq data for the estimation of evolutionary relationships amongst ten teleost fish species, using previously established phylogeny as a benchmark.ResultsThe number of orthologous SbfI RAD loci identified decreased with increasing evolutionary distance between the species, with several thousand loci conserved across five salmonid species (divergence ~50 MY), and several hundred conserved across the more distantly related teleost species (divergence ~100-360 MY). The majority (>70%) of loci identified between the more distantly related species were genic in origin, suggesting that the bias of SbfI towards genic regions is useful for identifying distant orthologs. Interspecific single nucleotide variants at each orthologous RAD locus were identified. Evolutionary relationships estimated using concatenated sequences of interspecific variants were congruent with previously published phylogenies, even for distantly (divergence up to ~360 MY) related species.ConclusionOverall, this study has demonstrated that orthologous SbfI RAD loci can be identified across closely and distantly related species. This has positive implications for the repeatability of SbfI RAD-Seq and its potential to address research questions beyond the scope of the original studies. Furthermore, the concordance in tree topologies and relationships estimated in this study with published teleost phylogenies suggests that similar meta-datasets could be utilised in the prediction of evolutionary relationships across populations and species with readily available RAD-Seq datasets, but for which relationships remain uncharacterised.
| S-EPMC4495686 | biostudies-literature
Project description:Prostate cancer is the most diagnosed cancer among men in the United States. While the majority of patients who undergo surgery (prostatectomy) will essentially be cured, about 30-40% men remain at risk for disease progression and recurrence. Currently, patients are deemed at risk by evaluation of clinical factors, but these do not resolve whether adjuvant therapy will significantly attenuate or delay disease progression for a patient at risk. Numerous efforts using mRNA-based biomarkers have been described for this purpose, but none have successfully reached widespread clinical practice in helping to make an adjuvant therapy decision. Here, we assess the utility of non-coding RNAs as biomarkers for prostate cancer recurrence based on high-resolution oligonucleotide microarray analysis of surgical tissue specimens from normal adjacent prostate, primary tumors, and metastases. We identify differentially expressed non-coding RNAs that distinguish between the different prostate tissue types and show that these non-coding RNAs can predict clinical outcomes in primary tumors. Together, these results suggest that non-coding RNAs are emerging from the "dark matter" of the genome as a new source of biomarkers for characterizing disease recurrence and progression. While this study shows that non-coding RNA biomarkers can be highly informative, future studies will be needed to further characterize the specific roles of these non-coding RNA biomarkers in the development of aggressive disease.
| S-EPMC3284255 | biostudies-literature
Project description:Background and objectivesThere is interest in applying genomic sequencing (GS) to newborns' clinical care. Here we explore parents' and clinicians' attitudes toward and perceptions of the risks, benefits, and utility of newborn GS compared with newborn screening (NBS) prior to receiving study results.MethodsThe BabySeq Project is a randomized controlled trial used to explore the impact of integrating GS into the clinical care of newborns. Parents (n = 493) of enrolled infants (n = 309) and clinicians (n = 144) completed a baseline survey at enrollment. We examined between-group differences in perceived utility and attitudes toward NBS and GS. Open-ended responses about risks and benefits of each technology were categorized by theme.ResultsThe majority of parents (71%) and clinicians (51%) agreed that there are health benefits of GS, although parents and clinicians agreed more that there are risks associated with GS (35%, 70%) than with NBS (19%, 39%; all P < .05). Parents perceived more benefit and less risk of GS than did clinicians. Clinicians endorsed concerns about privacy and discrimination related to genomic information more strongly than did parents, and parents anticipated benefits of GS that clinicians did not.ConclusionsParents and clinicians are less confident in GS than NBS, but parents perceive a more favorable risk/benefit ratio of GS than do clinicians. Clinicians should be aware that parents' optimism may stem from their perceived benefits beyond clinical utility.
| S-EPMC6480393 | biostudies-literature
Project description:ObjectiveAn understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in schools is important. It is often difficult, using epidemiological information alone, to determine whether cases associated with schools represent multiple introductions from the community or transmission within the school. We describe the use of whole genome sequencing (WGS) in multiple schools to investigate outbreaks of SARS-CoV-2 in the pre-Omicron period.Study designSchool outbreaks were identified for sequencing by local public health units based on multiple cases without known epidemiological links. Cases of SARS-CoV-2 from students and staff from 4 school outbreaks in Ontario underwent WGS and phylogenetic analysis. The epidemiological clinical cohort data and genomic cluster data are described to help further characterize these outbreaks.ResultsA total of 132 positive SARS-CoV-2 cases among students and staff from 4 school outbreaks were identified with 65 (49%) of cases able to be sequenced with high-quality genomic data. The 4 school outbreaks consisted of 53, 37, 21 and 21 positive cases; within each outbreak there were between 8 and 28 different clinical cohorts identified. Among the sequenced cases, between 3 and 7 genetic clusters, defined as different strains, were identified in each outbreak. We found genetically different viruses within several clinical cohorts.ConclusionsWGS, together with public health investigation, is a useful tool to investigate SARS-CoV-2 transmission within schools. Its early use has the potential to better understand when transmission may have occurred, can aid in evaluating how well mitigation interventions are working and has the potential to reduce unnecessary school closures when multiple genetic clusters are identified.
| S-EPMC9990487 | biostudies-literature
Project description:BackgroundIt is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents' experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU.MethodsParents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child's sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews.ResultsKey themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child's future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent-infant bonding, and reported variable impact on their feelings of guilt.ConclusionParents reported that GS during the neonatal period was useful because it provided a "backbone" for their child's care. Parents did not consistently endorse negative impacts like interference with parent-infant bonding.
| S-EPMC10382030 | biostudies-literature
Project description:The first highly pathogenic (HP) influenza A/H7N9 was reported in Guangdong in January 2017. To investigate the emergence and spread of HP A/H7N9 in Guangdong province, we sequenced 297 viruses (58 HP A/H7N9, 19 low pathogenic (LP) A/H7N9, and 220 A/H9N2) during 2016-2017. Our analysis showed that during the fifth wave, three A/H7N9 lineages were co-circulating in Guangdong: the local LP Pearl River Delta (PRD) lineage (13%), the newly imported LP Yangtze River Delta (YRD) lineage (23%), and the HP YRD lineage (64%). Previously circulating YRD-lineage LP during the third wave evolved to the YRD-lineage HP A/H7N9 in Guangdong. All YRD-lineage LP detected during the fifth wave most likely originated from newly imported viruses into Guangdong. Genotype comparison of HP A/H7N9 suggests limited outward spread of HP A/H7N9 to other provinces. The distribution of HP A/H7N9 cleavage site variants on live poultry markets differed from that found in humans, suggesting a V1-type cleavage site may facilitate human infections.
| S-EPMC7758296 | biostudies-literature
Project description:Effective management and control of parasitic infections on farms depends on their early detection. Traditional serological diagnostic methods for Fasciola hepatica infection in livestock are specific and sensitive, but currently the earliest detection of the parasite only occurs at approximately three weeks post-infection. At this timepoint, parasites have already entered the liver and caused the tissue damage and immunopathology that results in reduced body weight and loss in productivity. Here, we investigated whether the differential abundance of micro(mi)miRNAs in sera of F. hepatica-infected sheep has potential as a tool for the early diagnosis of infection. Using miRNA sequencing analysis, we discovered specific profiles of sheep miRNAs at both the pre-hepatic and hepatic infection phases in comparison to non-infected sheep. In addition, six F. hepatica-derived miRNAs were specifically identified in sera from infected sheep. Thus, a panel of differentially expressed miRNAs comprising four sheep (miR-3231-3p; miR133-5p; 3957-5p; 1197-3p) and two parasite miRNAs (miR-124-3p; miR-Novel-11-5p) were selected as potential biomarkers. The expression of these candidates in sera samples from longitudinal sheep infection studies collected between 7 days and 23 weeks was quantified using RT-qPCR and compared to samples from age-matched non-infected sheep. We identified oar-miR-133-5p and oar-miR-3957-5p as promising biomarkers of fasciolosis, detecting infection as early as 7 days. The differential expression of the other selected miRNAs was not sufficient to diagnose infection; however, our analysis found that the most abundant forms of fhe-miR-124-3p in sera were sequence variants (IsomiRs) of the canonical miRNA, highlighting the critical importance of primer design for accurate diagnostic RT-qPCR. Accordingly, this investigative study suggests that certain miRNAs are biomarkers of F. hepatica infection and validates miRNA-based diagnostics for the detection of fasciolosis in sheep.
2024-04-15 | GSE254115 | GEO
Project description:BackgroundDecision impact studies have become increasingly prevalent in cancer prognostic research in recent years. These studies aim to evaluate the impact of a genomic test on decision-making and appear to be a new form of evidence of clinical utility. The objectives of this review were to identify and characterize decision impact studies in genomic medicine in cancer care and categorize the types of clinical utility outcomes reported.MethodsWe conducted a search of four databases, Medline, Embase, Scopus and Web of Science, from inception to June 2022. Empirical studies that reported a "decision impact" assessment of a genomic assay on treatment decisions or recommendations for cancer patients were included. We followed scoping review methodology and adapted the Fryback and Thornbury Model to collect and analyze data on clinical utility. The database searches identified 1803 unique articles for title/abstract screening; 269 articles moved to full-text review.Results87 studies met inclusion criteria. All studies were published in the last 12 years with the majority for breast cancer (72%); followed by other cancers (28%) (lung, prostate, colon). Studies reported on the impact of 19 different proprietary (18) and generic (1) assays. Across all four levels of clinical utility, outcomes were reported for 22 discrete measures, including the impact on provider/team decision-making (100%), provider confidence (31%); change in treatment received (46%); patient psychological impacts (17%); and costing or savings impacts (21%). Based on the data synthesis, we created a comprehensive table of outcomes reported for clinical utility.ConclusionsThis scoping review is a first step in understanding the evolution and uses of decision impact studies and their influence on the integration of emerging genomic technologies in cancer care. The results imply that DIS are positioned to provide evidence of clinical utility and impact clinical practice and reimbursement decision-making in cancer care. Systematic review registration: Open Science Framework osf.io/hm3jr.
| S-EPMC10004522 | biostudies-literature