Clinical exome sequencing reports: current informatics practice and future opportunities

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine E.; Cole, Justin W.; Bartlett, Christopher W.; Lin, Simon

doi:10.1093/jamia/ocx048

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…Currently, the turnaround time of prenatal CMA is ~15 working days, although it can be shorter or longer depending on operational protocols in different labs. The turnaround time of clinical proband WES is around 12–15 weeks 35 , 36 , but the turnaround time can be reduced to 2–4 weeks using trio WES or rapid bioinformatics pipelines in situations requiring fast assessment, such as prenatal, neonatal, or pediatric intensive care diagnosis 35 , 37 . Indeed, 24 h trio-ES or 26 h WGS pipelines are available for critically ill infants 38 .…”

Section: Resultsmentioning

confidence: 99%

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing

et al. 2022

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Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.

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Section: Resultsmentioning

confidence: 99%

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing

et al. 2022

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“…29 Additionally, if a system receives results from multiple laboratory entities, each can have their own reporting format that can cause interoperability issues when consolidating data into the EHR. 30 In 2019, Health Level 7 updated the Fast Healthcare Interoperability Resources (FHIR 4) standard that reduces technology barriers to patient information from any data source including EHRs. One of the challenges of FHIR is the bidirectional sharing of information, for example, the app can retrieve data from the EHR to the user, but few-if any-EHRs are able to receive information from the app.…”

Section: Electronic Health Record Privacy and Genetic Resultsmentioning

confidence: 99%

Ethical Considerations on Pediatric Genetic Testing Results in Electronic Health Records

et al. 2020

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Background Advances in technology and access to expanded genetic testing have resulted in more children and adolescents receiving genetic testing for diagnostic and prognostic purposes. With increased adoption of the electronic health record (EHR), genetic testing is increasingly resulted in the EHR. However, this leads to challenges in both storage and disclosure of genetic results, particularly when parental results are combined with child genetic results. Privacy and Ethical Considerations Accidental disclosure and erroneous documentation of genetic results can occur due to the nature of their presentation in the EHR and documentation processes by clinicians. Genetic information is both sensitive and identifying, and requires a considered approach to both timing and extent of disclosure to families and access to clinicians. Methods This article uses an interdisciplinary approach to explore ethical issues surrounding privacy, confidentiality of genetic data, and access to genetic results by health care providers and family members, and provides suggestions in a stakeholder format for best practices on this topic for clinicians and informaticians. Suggestions are made for clinicians on documenting and accessing genetic information in the EHR, and on collaborating with genetics specialists and disclosure of genetic results to families. Additional considerations for families including ethics around results of adolescents and special scenarios for blended families and foster minors are also provided. Finally, administrators and informaticians are provided best practices on both institutional processes and EHR architecture, including security and access control, with emphasis on the minimum necessary paradigm and parent/patient engagement and control of the use and disclosure of data. Conclusion The authors hope that these best practices energize specialty societies to craft practice guidelines on genetic information management in the EHR with interdisciplinary input that addresses all stakeholder needs.

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“…At present, there is still uncertainty as to where this type of technology fits into clinical practice and to what extent if any the results of WES or WGS should be used when making decisions about a patient's treatment; however, there are emerging and encouraging reports of how this technology is being used in the clinical setting specifically for patients with CRC [97]. WES and WGS interpretation and reporting are still in its infancy, but we are beginning to see a push from informatic associations towards standardized reporting of WES and WGS much like a radiology report so that they can be easily interpreted and used in the clinical setting [98].…”

Section: Potential Applications Of Sequencing In the Future-whole Gen...mentioning

confidence: 99%

Clinical Oncogenomics and Personalized Medicine in Colorectal Cancer for the Surgeon: What We Need to Know and What the Future Holds

Reynolds

OʼConnell

McNamara

et al. 2022

SN Compr. Clin. Med.

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Changes in the normal nucleotide sequence of the human genome plays an integral part in the development and progression of all cancers. It is now recognized that certain genomic alterations can be used to determine prognosis and potential response to treatment for patients diagnosed with a range of cancers. Breast cancer is perhaps the best example of how gene expression analysis can influence treatment choices and potentially prevent patients from receiving adjuvant chemotherapy that would have a negligible benefit. It is becoming increasingly likely that most, if not all, tumors will be subjected to some form of genomic analysis in the future in an attempt to provide patients with a personalized treatment plan that maximizes efficacy and reduces toxicity. This paper gives a brief history of genomic sequencing followed by a description of clinically relevant oncogenomics for those working in the colorectal cancer field. The relevance of RAS, BRAF, mismatch repair, and microsatellite instability status are discussed in detail. Potential implications of PIK3CA mutations are briefly described. It finishes by providing a summary of more complex techniques such as whole exome and whole genome sequencing, some of which may be used in the clinical setting and some of which will be reserved solely for novel target and biomarker identification in the academic setting. An understanding of the molecular mechanisms that underlie the development and progression of colorectal cancer is necessary and will become more relevant as the practice of personalized medicine is more widely implemented.

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Clinical exome sequencing reports: current informatics practice and future opportunities

Cited by 11 publications

References 22 publications

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing

Ethical Considerations on Pediatric Genetic Testing Results in Electronic Health Records

Clinical Oncogenomics and Personalized Medicine in Colorectal Cancer for the Surgeon: What We Need to Know and What the Future Holds

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