Finally, I find the underlying R code in a file created by GrapheR. For more details read also the package vignette, which is available in English, French and German!

A recent study published in Genome Biology (https://link.springer.com/article/10.1186/s13059-026-04280-y) addressed this challenge by introducing dicast (https://github.com/burgshrimps/dicast), a machine-learning approach for detecting structural variants in short-read sequencing data. Structural variants, such as large deletions, insertions, duplications, and inversions, can have significant biological and clinical implications, yet they are challenging to identify with short-read technologies. Because different detection methods frequently yield divergent results, researchers commonly employ consensus calling, considering a variant valid only if multiple tools detect it. While this approach reduces false positives, it relies on the potentially flawed assumption that the majority is always correct.

The researchers explored the impact of evaluating the supporting evidence for each variant, rather than simply tallying the number of algorithms that identified it. To establish a ground truth, they analyzed nine genomes using multiple sequencing technologies and 15 detection methods, initially identifying approximately 35 million potential variants. Through extensive filtering, evidence integration, and manual review of over 11,500 variants, they developed a robust benchmark comprising more than 236,000 structural variants. The findings underscored the complexity of the problem: short-read methods detected fewer than half of deletions and less than 10 percent of insertions, with performance declining markedly in repetitive genomic regions. In contrast, long-read technologies demonstrated superior detection capabilities. However, replacing the substantial volume of existing short-read data in clinical and research settings is not immediately feasible. Consequently, the researchers questioned whether short-read data might harbor more information than conventional analytical pipelines currently extract.

This line of inquiry led to the development of dicast. Rather than merely confirming agreement among multiple tools, dicast identifies patterns in sequencing data, including split and clipped reads, discordant read pairs, alignment characteristics, and the surrounding genomic context. An XGBoost machine-learning model evaluates which combinations of these signals are indicative of genuine structural variants. Thus, the approach shifts from tallying algorithmic consensus to interpreting the underlying evidence.

The researchers subsequently conducted a targeted evaluation by examining structural variants detected by only a single short-read tool, which are typically missed by consensus-based approaches. dicast successfully recovered approximately 81% of these single-caller deletions, insertions, and duplications. The signals for these variants were present in the data, but conventional filtering methods failed to integrate them effectively.

The utility of dicast was further demonstrated in cohorts with rare diseases, including congenital limb malformations, atrial fibrillation, and neuromuscular disorders. In one instance, dicast achieved a deletion recall rate of approximately 0.96, compared to 0.74 using consensus calling. The median number of variants requiring manual review was 29 per sample. Among 31 experimentally validated variants that standard filters would have missed, dicast identified 12, whereas consensus calling detected only one.

Overall, dicast identified approximately 20 percent more potential disease-causing deletions than consensus-based methods. While a 20 percent increase may appear modest, in clinical genomics such improvements can have significant practical implications. Missing a deletion may leave a case unresolved, whereas detecting a structural variant can provide critical diagnostic insights.

The study does not claim that machine learning has rendered short-read sequencing superior to long-read approaches. Instead, the results underscore the effectiveness of long-read sequencing for structural variant detection. However, dicast highlights a more nuanced perspective: substantial biological information may still be recoverable from the extensive short-read datasets already available.

The principal lesson extends beyond the detection of structural variants. For many years, bioinformatics pipelines have relied on threshold-based criteria, such as minimum coverage, quality scores, or support from multiple tools. While these rules are useful, biological phenomena do not always conform to rigid checklists; multiple weak signals, when considered collectively, can provide compelling evidence.

This perspective prompts consideration of the solitary variant: one algorithm identifies it, while several others do not. Traditional consensus techniques might have dismissed it, yet machine learning approaches evaluate the available evidence to determine whether the variant is plausible.

Occasionally, the most significant variant within a genome is the one that is almost universally overlooked.

Read more at https://link.springer.com/article/10.1186/s13059-026-04280-y

More at http://pythonhosted.org/pybedtools/

A powerful toolset for genome arithmetic.http://code.google.com/p/bedtools/

minimap -t 24 assembly.fasta long_reads.fastq.gz | racon -t 24 long_reads.fastq.gz - assembly.fasta racon_assembly.fasta
nucmer -p nucmer assembly.fasta racon_assembly.fasta
show-snps -C -T -r nucmer.delta

This reports Racon's changes in a table. You can exclude indels with the -I option in show-snps. 

This process (Racon -> MUMmer -> SNP table) solves the problem I originally raised in this issue. So as far as I'm concerned, you can close this issue (or keep it open if you still want to implement some kind of variant table).

We accomplish this by first calculating genotype likelihoods for every site. For a given site in a diploid genome, there are 10 possible genotypes (AA, AC, AG, AT, CC, CG, CT, GG, GT, TT). Referee takes as input the genotype likelihoods calculated for all 10 genotypes given the called reference base at each position.

Referee is a program to calculate a quality score for every position in a genome assembly. This allows for easy filtering of low quality sites for any downstream analysis.

https://github.com/gwct/referee

Address of the bookmark: https://gwct.github.io/referee/#

This job will allow the intern to become more familiar with new biological and bioinformatics tools like next generation sequencing, RNA-Seq data analysis and comparative genomics.

To apply for this position, send the following documents (in PDF format) to Dr Pierre-Yves Dupont (email p.y.dupont@massey.ac.nz):

1. A short cover letter.
2. A curriculum vitae, with transcript details.
3. The names and contact details of two referees willing to provide a confidential letter of recommendation upon request.

Informal enquiries are welcome. Formal applications are due by Sunday 2nd December 2012.
Requirements:

This position requires a good understanding of genetic problems, a good command of at least one scripting language (Perl, Python...), a basic knowledge of MySQL or any relational database management system. Knowledge in biological programming libraries (BioPython, BioPerl, BioRuby...), Java, C++ or any compiled language is an asset but not required. Undergraduate or Master degree is required.
Contact Information:

Dr. Pierre-Yves Dupont
Institute of Molecular BioSciences
Massey University
Private Bag 11 222
Palmerston North 4442
NEW ZEALAND

http://massey.genomicus.com/
p.y.dupont@massey.ac.nz

Information about the Institute of Molecular BioSciences (http://imbs.massey.ac.nz/) and the Computational Biology Research Group (http://massey.genomicus.com/) is available online. For more information about the position, you can contact Dr Pierre-Yves Dupont (email p.y.dupont@massey.ac.nz).

A swift, versatile phylogenomic and high-throughput sequencing simulator https://jackalope.lucasnell.com

Address of the bookmark: https://github.com/lucasnell/jackalope

The candidate will be mainly in charge of developing research on Gene Expression/SNP Arrays data, NGS whole -exome and -transcriptome datasets and biological networks in the contexts of genetic diseases, innovative therapies and regenerative medicine. Main activities will be: (i) data analysis (short-reads mapping, genomics aberrations discovery and annotation, variants pathogenicity detection); (ii) functional/pathway enrichment analysis; (iii) biological networks analysis (artificial knockout, redundancy and lethality analysis, gene set essentiality); (iv) developing of ad-hoc software solutions/routines on clusters of CPUs and GPUs.

The correct cultural background (training in Biology / Computer Science / Statistics or a mix of the three) and a strong interest in working in high throughput data analysis will be considered at the same level of specific experience in the above-mentioned fields.

Knowledge of molecular modeling and simulation and willingness to learn one or more of these languages: python, perl, R, Java, C++, C# is a golden plus. Good knowledge of Scientific English will be positively evaluated for this position, together with good presentation and teamwork skills.

Candidates should send:
• a cover letter explaining the role they would like to undertake within the Center, even if it is not listed in this job adv, stating clearly why they would be a good fit to the proposed role, and what they would bring to the Center in terms of expertise, ideas, talent;
• a CV including a list of publications;
• List of referees.

A CV with one professional reference, details on educational background and of the biological and/or bioinformatic and/or data analysis skills and experience should be sent by email for a preliminary selection to: Tommaso Mazza t.mazza@css-mendel.it

More at https://kevlar.readthedocs.io/en/latest/

https://www.cell.com/iscience/pdf/S2589-0042(19)30259-7.pdf

Address of the bookmark: https://github.com/kevlar-dev/kevlar