Software for analysis of cell-free DNA (cfDNA)

Below is the repository of software tools for analysis of sequenced cell-free DNA (cfDNA). This collection is part of NucPosDB, a manually curated database of experimental nucleosome maps in vivo, cfDNA and computational tools related to nucleosome positioning

**How to cite: Shtumpf M., Piroeva K.V., Agrawal S.P., Jacob D.R., Teif V.B. (2022). NucPosDB: a database of nucleosome positioning in vivo and nucleosomics of cell-free DNA. Chromosoma 131, 19-28 | open access article

Name	Key features	Programming language	Analysis type	Citation
BIC-seq2	Normalization oh high-throughput sequencing (HTS) data and detect CNVs with or without a control gene. Avoids high variability of reads in the bins.	Shell	Copy number variations	Xi et al., 2016
CancerDetector	Improves ctDNA fraction estimation and identifies outliner markers.	R	Methylation	Li et al., 2018
CancerLocator	Simultaneously infers the proportion and tissue of origin of ctDNA.	Java	Methylation	Kang et al., 2017
CELFIE	Estimates cell type proportion from both whole genome cfDNA input and reference data. Do not rely on CpG site curation, estimates unknown cell types that are not available in reference. Estimate known and unknown cell type in low coverage and noisy data.	Python	DNA methylation	Caggiano et al., 2020
cfCHIP-seq	ChIP–seq offers superior data quality to chromatin immunoprecipitation and eliminate bias in fragmentation and sequencing.	R	DNA-binding proteins and histone modifications	Sadeh et al., 2021
cfDNA-FEP	cfDNA fragment end profiling in genomic regions of interest	R	cfDNA fragmentation profiles	Zhitnyuk et al., 2022
cfDNApipe	Accompanied with a GC-bias correction approach, distinguishes differential methylation regions between subject and control samples	Python	Copy number variations, DNA methylation, Nucleosome positioning	Ahang et al., 2021
CNAclinic	carry out an analysis of CNA providing functionality tailored for shallow whole genome sequencing as well as the capacity for multi-faceted visualization and data interrogation.	R	DNA fragmentation and CNVs	Mouliere et al., 2018
CNVkit	Targeted re-sequencing, which leaves gaps in coverage between the regions chosen for enrichment and introduces biases. Uses both the targeted reads and the non-specifically captured off-target reads to infer copy number.	Python	Copy number variations	Talevich et al., 2016
DeepSNV	Detection of subclonal single nucleotide variants in heterogenous cell populations.	Python	Somatic mutation	Gerstung et al., 2012
DELFI	Detection of the abnormalities of cfDNA fragmentation profiles at genome-wide level	R	Nucleosome positioning	Cristiano et al., 2019
Griffin	A flexible framework for nucleosome profiling of cell-free DNA	Python	Nucleosome positioning	Doebley et al., 2021
ichorCNA	Estimating tumor fraction in cell-free DNA from ultra-low-pass whole genome sequencing.	R, Shell	Tumor fraction	Adalsteinsson et al., 2017
INVAR	Combines locus-based noise filtering, strand selection, and enrichment of mutant fragments using biological characteristics of ctDNA. The detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci.	Python, R	Somatic mutation	Wan et al., 2020
JointSN-VMix	Germline and somatic events can be identified and distinguished.	Python, C	Somatic mutation	Roth et al., 2012
MAGERI	An efficient pipeline for analysis of unique molecular identifier or UMI-encoded data by filling the gaps.	Java	Ultra-rare somatic mutation	Shugay et al., 2017
MRDetect	Allows genome-wide mutational integration, enabling ultra-sensitive detection		Somatic mutation	Zviran et al., 2020
MSIsensor-ct	Detection of microsatellite instability (MSI) status in cfDNA sequencing data with MSIscore threshold of 20%.	C++	Microsatellite Instability (MSI)	Han et al., 2021
Mutation-Seq	Feature-based classification. Integrate different features like base qualities, mapping qualities, strand bias, and tailed distance features.	Python, C++, C	Somatic mutation	Ding et al., 2012
MutTect	High sensitivity	Java	Somatic mutation	Cibulskis et al., 2013
NDRquant	Quantification of the content of circulating tumor DNA (ctDNA) based on tissue-specific cfDNA degradation of nucleosome depleted regions (NDR).	Shell	Nucleosome Positioning	Zhu et al., 2021
NucTools	Analysis of chromatin feature occupancy profiles from high-throughput sequencing data	Perl, Shell, R ,CSS	Nucleosome positioning	Vainshtein et al., 2017
PlasmaSeq	Estimates tumor fraction in cell-free DNA from ultra-low-pass whole genome sequencing	R, HTML, C, Perl, TeX, CSS, Other	Tumor fraction	Moser et al., 2017
Python Scripts	Analysis of epigenetic signals captured by fragmentation patterns of cfDNA and develop in vivo nucleosome footprint that informs TOO.	Python	Nucleosome positioning	Snyder et al., 2016
QDNA-seq	Whole-genome sequencing (WGS) faces lack of completion and errors in human reference genome and has biases in the sequencing procedure. Simultaneously corrects Sequence mappability and GC content biases.	R	Copy number variations	Scheinin et al., 2014
Seurat	Detection of cancer related different somatic events of point mutations such as base substitution, insertion and deletion. Detection of loss of heterogenicity events, translocations and large deletions.	R	Somatic mutation	Christoforides et al., 2013
Shimmer	Prediction of SNVs with high sensitivity and accuracy in highly contaminated or heterogenous samples.	Python, R, C	Somatic mutation	Hansen et al., 2013
SomaticSniper	Compares and identifies the unique (mutation) sites in tumour and normal pairs of samples.	Python, C	Single nucleotide variants	Larson et al., 2012
Spiky	Converts read counts to picomoles of DNA fragments, while adjusting for fragment properties that affect enrichment.	R, Makefile	Spike-in DNA controls	Wilson et al., 2021
Strelka	Enable detection of longer somatic indels and open break ends in contigs obtained from the routine de-novo assembly.	Python, C++	Somatic mutation and copy number variations	Saunders et al., 2012
TranscriptionFactorProfiling	Profiling of transcription factor binding sites in cell-free DNA	Python, R, Shell	Transcription factor profiling	Ulz et al., 2019
UMI-tools	Low ctDNA content and sequencing artefacts limit analytical sensitivity. To overcome this, unique molecular identifiers (UMIs) are added into the adapters to tag individual cfDNA. UMI-tools identifies sequencing errors in the UMI sequences by comparing the sequences of PCR duplicates with UMI sequences to improve quantification accuracy.	Python	Somatic mutation	Smith et al., 2017
VarScan2	Detection of somatic mutations and copy number alterations in tumour and normal pairs of samples.	Python, R	Single nucleotide variants	Koboldt et al., 2012
WisecondorX	Optimization of segmentation by reducing noise from problematic bins and lowering computing time.	Python, R	Copy number variations	Raman et al., 2019
LIQUORICE	Detection of epigenetic signatures in liquid biopsies based on whole-genome sequencing data	Python, Shell	Epigenetic signatures	Peneder, Bock and Tomazou, 2022
iWhale	Computational pipeline for detection and annotation of somatic variants in cancer WES data	Python, Dockerfile	Somatic mutation	Binatti et al., 2021
MSK-GRAIL-TECHVAL	High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants	R	Copy number variations	Razavi et al., 2019