Benjamin S-B 
🎉New preprint out today! We present rastair - an ultra-fast SNP and methylation caller for TAPS or 5-Base data. Rastair takes less than 1h to process e.g. a 50x 5-Base dataset, yet SNP call accuracy is nearly identical to GATK on WGS data 🔥
https://www.biorxiv.org/content/10.64898/2026.03.19.712983v1
Rastair: an integrated variant and methylation caller
Cytosine methylation is a crucial epigenetic mark that impact tissue-specific chromatin conformation and gene expression. For many years, bisulfite sequencing (BS-seq), which converts all non-methylated cytosine (C) to thymine (T), remained the only approach to measure cytosine methylation at base resolution. Recently, however, several new methods that convert only methylated cytosines to thymine (mC→T) have become widely available. Here we present rastair, an integrated software toolkit for simultaneous SNP detection and methylation calling from mC→T sequencing data such as those created with Watchmaker's TAPS+ and Illumina's 5-Base chemistries. Rastair combines machine-learning-based variant detection with genotype-aware methylation estimation. Using NA12878 benchmark datasets, we show that rastair outperforms existing methylation-aware SNP callers and achieves F1 scores exceeding 0.99 for datasets above 30x depth, matching the accuracy of state-of-the-art tools run on whole-genome sequencing data. At the same time, rastair is significantly faster than other genetic variant callers, processing a 30x depth file takes less than 30 minutes given 32 CPU cores on an Intel Xeon, and half as long when a GPU is available. By integrating genotyping with methylation calling, rastair reports an additional 500,000 positions in NA12878 where a SNP turns a non-CpG reference position into a "de-novo" CpG. Vice-versa, rastair also identifies positions where a variant disrupts a CpG and corrects their reported methylation levels. Rastair produces standard-compliant outputs in vcf, bam and bed formats, facilitating integration into downstream analyses pipelines. Rastair is open-source and available via conda, Dockerhub, and as pre-compiled binaries from https://www.rastair.com. ### Competing Interest Statement Pascal Hertleif is a employee and owner of Softleif AB, a software development company. All other authors declare no competing financial interests. Ludwig Institute For Cancer Research
Geert Aarts
Infodoc MicroVeille
Stephen Royle
Hazletok
Daniel Prieto
Jocelyn Etienne
Cosmin Saveanu
petersuber
Ko-Fan Chen 陳克帆