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Archive of posts filed under the General category.

PEDIA’s Machine Learning Challenge

We used 155 cases with a molecularly confirmed diagnosis of a monogenic disease and annotated the following five scores for every gene with a rare variant in the exome: gestalt-score, feature-score, pheno-score, boqa-score, cadd-score, The gestalt score is based on image analysis from Face2Gene. Feature-, pheno- and boqa- scores are based on a deep phenotypic […]

PEDIA study: Prioritization of Exome Data by Image Analysis

Interpreting thousands of sequence variants from an exome analysis is challenging, especially if only the data of the patient itself is available and no more family members can be used for filtering. In such cases a detailed description of the phenotypic findings is the key for prioritizing candidate mutations. In patients with dysmorphic features automated […]

Non-coding variant interpretation using GeneTalk

Variants in noncoding regions are always difficult to interpret on a genomic level . In a recently published article in Human Mutation entitled “Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of HPMRS“ we present an approach for filtering pathogenic nonconding variants and explain how to interpret the implications of the variants […]

pLI score

Many of you perform trio exome sequencing to detect de novo mutations in an affected individual. This is for a good reason, as we all know that the probability of a coding DNM to be disease-causing is very high. However, sometimes there are more than a single loss-of-function DNM in an exome, or the gene […]

Analyzing Family Exome Data …

When you ask two laywers for their opinion you might get three different answers. In genetics it could get even worse: Corpas et al. analyzed four publicly available exomes of a family with different software tools. Surprisingly there was only little overlap in the sequence variants that were assessed as clinically relevant. We would like […]

Allele balance filter

The allele balance is defined as the ratio of reads that support the alternative allele in a next-generation sequencing data set. In a usual vcf file this ratio can be computed by the information encoded in the AD, AO, and DP flag. For heterozygous genotypes and especially de novo calls the allele balance is also […]

Rare Variant Association Studies

Yippie, our new paper about rare variant association studies, RVAS, just appeared in Bioinformatics! In this work we describe strategies to optimise the probability to detect the disease-causing mutations in a cohort of patients. Obviously, the detection power depends on the size of your case group and the genetic variability of the true disease gene. […]


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The frequency filter Hardy Weinberg dreamed of

You are suspecting a recessive mode of inheritance. What cutoff for the frequency filter should you select? Well, it depends, are you looking for a homozygous pathogenic mutation or compound heterozygotes? This makes a big difference and the Hardy-Weinberg principle might help you to decide. Let’s review the math: In a sufficiently large population there […]

Poll about Gene Panel Usage

Hello everyone, Gene Panels comprising hundreds of genes are getting more and more popular for analyzing patients with rare inherited disorders. Currently enrichment or amplification kits of Agilent SureSelect, Illumina TruSight, and Ion Torrent AmpliSeq seem to be most widely used. We are working on a really great new feature that will make it almost […]