The Curation of Genetic Variants: Difficulties and Possible Solutions

Abstract

The curation of genetic variants from biomedical articles is required for various clinical and research purposes. Nowadays, establishment of variant databases that include overall information about variants is becoming quite popular. These databases have immense utility, serving as a user-friendly information storehouse of variants for information seekers. While manual curation is the gold standard method for curation of variants, it can turn out to be time-consuming on a large scale thus necessitating the need for automation. Curation of variants described in biomedical literature may not be straightforward mainly due to various nomenclature and expression issues. Though current trends in paper writing on variants is inclined to the standard nomenclature such that variants can easily be retrieved, we have a massive store of variants in the literature that are present as non-standard names and the online search engines that are predominantly used may not be capable of finding them. For effective curation of variants, knowledge about the overall process of curation, nature and types of difficulties in curation, and ways to tackle the difficulties during the task are crucial. Only by effective curation, can variants be correctly interpreted. This paper presents the process and difficulties of curation of genetic variants with possible solutions and suggestions from our work experience in the field including literature support. The paper also highlights aspects of interpretation of genetic variants and the importance of writing papers on variants following standard and retrievable methods.

GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort

“…The curation of variants performed in the present work highlights the importance of specialized guidelines to analyze and interpret variants for the clinical use of databases. Moreover, it indicates the need of scientific community interaction and data sharing to avoid or reduce difficulties in variant curation [ 104 , 105 ]. Manual curation, although time consuming is strictly needed, as shown for the p.Met163Leu variant, which was originally interpreted as pathogenic for autosomal dominant HL by one submitter, and now reclassified to uncertain significance.…”

Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias

“…These complexities need to be taken into account when tracking VAF in patient leukemia and PDX models as well as of host mouse strain, which can also influence engraftment of particular hematopoietic lineages 32, 33 . Targeted sequencing coupled with manual curation allows exclusion of false variants that result from low-quality alignment, from low-quality reads, or from belonging to noisy genomic regions 34 . This is one of the benefits of targeted sequencing as manual curation of the whole exome or genome variants is likely to be overly laborious.…”

Pragmatic and Ethical Challenges of Incorporating the Genome into the Electronic Health Record

“…However, “traditional” nomenclature systems defined by early publications have been carried over in the literature and are used by many laboratories for certain variants, resulting in inconsistent referencing of variants. 42,43 Even if the genomics community fully committed to the HGVS nomenclature, the intricacy of the genome may preclude a fully computable naming system that would simultaneously provide unique identifiers for every possible variant. Without a standard way to reference a patient's variant in the EMR, systematic storage and retrieval of genomic data becomes difficult.…”