Awesome Linked Reads

This is a collection of tools and resources for analysis and processing of linked-reads.

• Tools
• Linked Read Platforms

Tools

Name	Category	Description	Last commit
Aldy	structural variants, variant calling	Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes
Ambigram	structural variants	Detection of complex breakage-fusion-bridge genome rearrangements that supports linked-reads
Aquila	assembly, pipeline	Diploid personal genome assembly and comprehensive variant detection based on linked-reads
Aquila_stLFR	assembly, pipeline	Human haplotype-resolved assembly and variant detection for stLFR, hybrid assembly for linked-reads
AquilaDeepFilter	structural variants	Deep learing based filtering of genome-wide false positive large deletions
AquilaSV	structural variants, variant calling	Structural variant detection from region-based phased diploid assemblies for 10X and stLFR linked-reads
ARBitR	scaffolding	ARBitR is an overlap aware genome assembly scaffolder for linked sequencing reads.
Ariadne	assembly, metagenomics	de Bruijn graph-based program for barcoded read deconvolution
arcs	assembly	Scaffold genome sequence assemblies.
Athena	assembly, metagenomics	Read cloud assembler for metagenomes
BarCrawler	qc	QC package for 10X genomics barcoded reads.
bcctools	toolkit	Correcting barcodes in 10X linked-read sequencing data
bcmap	mapping, toolkit	Fast tool to map approximate genome locations for barcoded molecules
BLR	pipeline	An end-to-end Snakemake workflow for whole genome haplotyping and structural variant calling from FASTQs from multiple linked-read technologies.
bxtools	toolkit	Tools for analyzing mapped 10x data
cloudSPAdes	assembly	Assembly of synthetic long reads using de Bruijn graphs
ChromeQC	qc	Summarize sequencing library quality of 10x Genomics Chromium linked reads
Cue	structural variants	Deep learning framework for SV calling and genotyping
DrLink	structural variants	Detecting recombination breakpoints using Linked read sequencing
EMerAld (EMA)	mapping	Preforms barcode-aware alignment of linked reads. Also does preprocessing of 10x Genomics data.
Gemtools	toolkit	Tools for working with linked-read sequencing (10X Genomics) data
grocsvs	structural variants	Genome-wide reconstruction of complex structural variants
HapCUT2	phasing	Phasing of barcode linked reads
HapTree-X	phasing	Haplotype phaser for next-generation sequencing data
HARPY	pipeline	Process raw haplotagging data, from raw sequences to phased haplotypes, batteries included.
HAST	assembly	Haplotype-Resolved Assembly for Synthetic Long Reads Using A Trio-Binning Strategy
Lancet	variant calling	Microassembly based somatic variant caller for linked-read data
Lariat	mapping	Linked-Read Alignment Tool
LEVIATHAN	structural variants	Linked-reads based structural variant caller with barcode indexing
Link_STR	toolkit	Analysis scripts developed for genotyping STRs in linked-read data
LinkedSV	structural variants	Structural variant caller for linked-read sequencing data
Linker	toolkit	Tools for analyzing long and linked read sequencing
LongRanger	pipeline	Pipeline for alignment, variant calling, phasing, and ptructural variant calling
LRez	toolkit	Standalone tool and library allowing to work with barcoded linked-reads
LRTK-SIM	simulation	A program to simulate linked reads sequencing from 10X Chromium System
LRSIM	simulation	A simulator for linked reads
MetaTrass	assembly	Taxonomic Reads Assembly For a Single Species to Metagenomics
Minerva	assembly	Sort Linked Read DNA Into Fragment Specific Clusters
mLinker (alt)	phasing, tookit	Tools for Determining Haplotype Phase from Long/Linked Read Sequencing
MTG-Link	assembly	Novel gap-filling tool for draft genome assemblies, dedicated to linked read data
NAIBR (original) NAIBR (fork)	structural variants	Identifies novel adjacencies created by structural variation events such as deletions, duplications, inversions, and complex rearrangements
Novel-X	structural variants	Novel insertion detection with 10X reads
NPGREAT	assembly	A hybrid assembly method that utilizes Nanopore and Linked-Reads datasets for the assembly of the human subtelomere regions.
Pangaea	assembly, metagenomics	A metagenome assembler for the linked-reads with high-barcode specificity
proc10xG	toolkit	Collection of scripts for processing 10x genomics reads
Pseudoseq	simulation	Fake genomes, fake sequencing, real insights.
Pyslr	assembly	Construct a Physical Map from Linked Reads
QuickDeconvolution	assembly	Quick and scalable software to deconvolve read clouds from linked-reads experiments without a reference genome
Samovar	variant calling	Somatic (mosaic) SNV caller for 10X Genomics data using random forest classification and feature-based filters
samplot	structural variants	Plot structural variant signals from many BAMs and CRAMs
Scaff10x (v5) Scaff10x (≤v4.1)	assembly	Pipeline for scaffolding and breaking a genome assembly
SpecHLA	phasing	Reconstructs entire diploid sequences of HLA genes and infers LOH events
SpLitteR (alt)	assembly	Repeat resolution in assembly graph using synthetic long reads
stLFRdenovo	assebly	De Novo assembly pipeline to deal with barcoded reads. It is based on Supernova, with a fastq parsing and sorting module constumized for stLFR data.
stLFRsv	structural variants	Structure variation(SV) pipeline for stLFR co-barcode reads
SuperNova	assembly	10x Genomics Linked-Read Diploid De Novo Assembler
SVenX	structural variants	Pipeline for SV detection using 10X genomics data
tenx_utils	toolkit	Utility functions for 10x data
Tigmint	assembly	Correct misassemblies using Linked Reads
TitanCNA_10x	pipeline,structural variants,cancer	Snakemake workflow for 10X Genomics WGS analysis using TitanCNA
Topsorter	structural variants, qc	Graphic assement of structural variants
VISOR	simulation	VarIant SimulatOR for short, long and linked reads
Valor	structural variants	Variation discovery using long range information in linked-reads
WhatsHap	phasing,qc,toolkit	Read-based phasing of genomic variants, also called haplotype assembly. Implements several tools which work with linked reads
Wrath	structural variants,qc	Visualisation and identification of candidate structural variants (SVs) from linked read data
xTea	structural variants	Comprehensive TE insertion identification
ZoomX	structural variants	Single Molecule Based Rearrangement Analysis with Linked Read Sequencing

Linked Read Platforms

10x Genomics Chromium / GemCode

10x Genomics linked-read technology comes in two versions; the older GemCode (v1) and more recent Chromium Genome (v2). Long DNA fragments are combined in droplets with barcode-containing gel-beads to create GEMs ((Gel Bead-In EMulsions). The fragments are amplified and barcoded using a combination of free random hexamers and barcode-linked random hexamers from the gel beads. Following this barcoded fragments are recovered and fragments before ligation of 3' sequencing adaptor. Libraries are sequenced using Illumina Sequencing. The commercial version of the technology is currently discontinued.

TELL-Seq

TELL-seq is based on the technology from Chen et al. 2020 and is commercially available from the company Universal Sequencing. The method uses clonaly barcode beads with attacted tagmentases to cut and barcode individual long DNA fragments in solution. A second tagmentation is also preformed in solution to introduce a second adaptor. The library is sequenced using Illumina sequencing with special setup to sequence the barcode as index 1.

stLFR

stLFR (single-tube long fragment read) is based on the technology described in Wang et al. 2019 and is commercially available from MGI. The technology uses tagmentation to individually cut-and-hold long DNA fragments in solution. The tagmentase-DNA complex is then hybridized and individual wrapped around barcoded beads through the adaptor introduced by the tagmentation. The barcode is then ligated to each subfragment before recovery and final library prepration. Sequencing is preformed on the DNBSEQ platfroms.

DBS

Droplet Barcode Sequencing (DBS) is based on the technology described in Redin el al. 2019. Long DNA fragments are subjected to tagmentation using Tn5-covered beads to cut, tag and wrap the fragment around the beads. The DNA-wrapped beads are then used in emmulsion PCR along with barcoded oligo. Within each emmulsion droplet the barcode and tagged fragments are amplified independently and then linked using overlap-extension. Barcode-linked fragments are recovered and indexed for Illumina sequencing.

CPT-seq

Technologies based Amini et al. 2014 and the follow-up CPTv2-seq from Zhang et al. 2017. These technologies were developed by Illumina but are not commercially available.

Haplotagging

Haplotagging is based on the technology presented in Meier et al. 2021. The technology uses barcoded beads covered with Tn5 tagmentase to cut and barcode individual long DNA fragments in solution. The beads are coated in a combination of two barcodes AB and CB that become inserted at the 5' and 3' of each cut fragment. Barcodes are combinatorialy generated with about 85 million possible combinations in total.

Contributions

Is some linked-read related tool missing from this resource? Either create a new issue with information about the tool you want to add or submit a pull request with the addition directly.

Credits

Inspired by the collection in Awesome-10x-genomics.