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

Pondicherry University Puducherry has been identified as a nodal agency by the Department of Biotechnology, Govt. of India to coordinate this examination along with nine centres namely, Pune University, Pune; Anna University, Chennai; Calcatta University (WBUT) Kolkata; Institute of Bioinformatics & Applied Biotechnology, Bangalore; North-Eastern Hill University, Shillong, University of Hyderabad, Hyderabad; University of Kerala, Thiruvananthapuram; Jawaharlal Nehru University, New Delhi and Assam Agricultural University, Guwahati.

In the BINC 2013 examination,17 candidates were certified. DBT has agreed to fund Research fellowships for all the BINC qualified Indian nationals to pursue Ph.D. in Indian Institutes/Universities. Note that the candidate must possess a postgraduate degree(or equivalent) & meet the criteria of the institutes/universities in order to avail research fellowship. In addition, cash prize of Rs. 10,000/- will be awarded to the top 10 BINC qualifiers.

More at http://210.212.230.224:9999/BINC/

https://www.youtube.com/watch?v=WgufqYMHCvM

Address of the bookmark: http://www.atgc.org/PhyloGrapher/PhyloGrapher_Welcome.html

Applications with complete bio-data from candidates possessing the required qualifications are invited for the posts of JRF (2) and Project Assistant (1) in

DBT, GOI-funded research project “Next Generation Sequencing (NGS)- based de novo assembly of expressed transcripts and genome information of Orchids in North-East India” in DBT’s Twinning programme for NE as per DBT sanction order and norms.

(i) JRF(2 nos.):

Qualifications: M.Tech/M.Sc in Life Sciences/ Botany/ Zoology/Biochemistry/ Biotechnology/ Bioinformatics; Desirable: Aptitude for Bioinformatics and Computer Programming/ Next generation sequencing data analysis

(ii) Project Assistant (1 no.):

Qualifications: Graduation in Science, Desirable: Experience of working in a Life Science/Plant Biotechnology lab. and familiarity with computers and field work viz. collection of samples.

The applications through email bicnehu@gmail.com or post must reach the undersigned
within 15 days from the date of publication of this advertisement. The advertised posts are purely temporary for the duration of the project and subject to availability of the funds from DBT. The appointment does not confer any entitlement or right over the posts for absorption in the University service.

Advertisement: www.nehu.ac.in/Advertisements/BICAdvtPV_200115.pdf

Organiser: Christine Carrington (University of the West Indies - UWI, St. Augustine, Trinidad and Tobago)
Co-organisers: Anne-Mieke Vandamme, Philippe Lemey (Katholieke Universiteit Leuven, Belgium), Marco Salemi, Mattia Prosperi (University of Florida, Gainesville, USA) and Karen E. Nelson (J. Craig Venter Institute, Rockville, USA)

Requests for information directly to:
Christine Carrington
Department of Preclinical Sciences
Faculty of Medical Sciences
University of the West Indies (UWI)
St. Augustine
Trinidad and Tobago
Telephone: +1-868-6452640 ext. 5009, +1-868-6848803
Fax: +1-868-6621873
E-mail: veme2015@sta.uwi.edu

Deadline for receipt of applications by local organiser: 15 March 2015
CALL FOR APPLICATIONS NOW OPEN
http://www.icgeb.org/course-application-trinidad-and-tobago-2015.html

http://rega.kuleuven.be/cev/veme-workshop/2015

For further details about the original technique see the UpSet website. You can also check out the UpSetR shiny app. Here is the source code for the shiny wrapper.

A Python package called py-upset to create UpSet plots has been created by GitHub user ImSoErgodic.

Address of the bookmark: https://github.com/hms-dbmi/UpSetR/

The entire book is written in R Markdown, using RStudio as my text editor and the bookdown package to turn a collection of markdown documents into a coherent whole. The book’s source code is hosted on GitHub, at https://github.com/clauswilke/dataviz. 

Address of the bookmark: https://clauswilke.com/dataviz/