ReviewBriefings in bioinformatics2024
Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges.
Review in Briefings in bioinformatics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- A systematic review on the generative AI applications in human medical genetics.Frontiers in genetics · 2025Pooled it
- Optimizing GRIDSS for clinical use: A targeted NGS filtering strategy for germline structural variant detection.European journal of human genetics : EJHG · 2026Article
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 2026Article
- A global survey of systems biology-based predictions of gene-rare disease associations to enhance new diagnoses.Scientific reports · 2026Article
- Fifteen Years of the Genome Analysis Toolkit as the De Facto Standard in Short-Read Variant Calling.International journal of molecular sciences · 2026Review
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- OctopuSV and TentacleSV: a one-stop toolkit for multi-sample, cross-platform structural variant comparison and analysis.Bioinformatics (Oxford, England) · 2025Article
- OctopuSV and TentacleSV: a one-stop toolkit for multi-sample, cross-platform structural variant comparison and analysis.Bioinformatics (Oxford, England) · 2025Article
- In Silico Characterization of Sirtuins in Acetic Acid Bacteria Reveals a Novel Phylogenetically Distinctive Group.Molecules (Basel, Switzerland) · 2025Article
- Comparative evaluation of four exome enrichment solutions in 2024: Agilent, Roche, Vazyme and Nanodigmbio.BMC genomics · 2025Article
- PLoV: a comprehensive database of genetic variants leading to pregnancy loss.Database : the journal of biological databases and curation · 2025Article
- Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.International journal of molecular sciences · 2024Article
- Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 7452 exome samples.National science review · 2024Article
- Major Causes of Conflicting Interpretations of Variant Pathogenicity in Rare Disease: A Systematic Analysis.Journal of personalized medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Next-generation sequencing (NGS) has revolutionized the field of rare disease diagnostics. Whole exome and whole genome sequencing are now routinely used for diagnostic purposes; however, the overall diagnosis rate remains lower than expected. In this work, we review current approaches used for calling and interpretation of germline genetic variants in the human genome, and discuss the most important challenges that persist in the bioinformatic analysis of NGS data in medical genetics. We describe and attempt to quantitatively assess the remaining problems, such as the quality of the reference genome sequence, reproducible coverage biases, or variant calling accuracy in complex regions of the genome. We also discuss the prospects of switching to the complete human genome assembly or the human pan-genome and important caveats associated with such a switch. We touch on arguably the hardest problem of NGS data analysis for medical genomics, namely, the annotation of genetic variants and their subsequent interpretation. We highlight the most challenging aspects of annotation and prioritization of both coding and non-coding variants. Finally, we demonstrate the persistent prevalence of pathogenic variants in the coding genome, and outline research directions that may enhance the efficiency of NGS-based disease diagnostics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.