
What is CrossMap ?¶
CrossMap is a program for genome coordinates conversion between different assemblies (such as hg18 (NCBI36) <=> hg19 (GRCh37)). It supports commonly used file formats including BAM, CRAM, SAM, Wiggle, BigWig, BED, GFF, GTF, MAF and VCF/gVCF.
How CrossMap works?¶

Release history¶
08/14/2020: Release version 0.5.0
Add CrossMap.py region
function to convert large genomic regions. Unlike the CrossMap.py bed
function which splits big genomic regions, CrossMap.py region
try to convert the big genomic region as a whole.
07/09/2020: Release version 0.4.3
Structural Variants VCF files often use INFO/END field to indicate the end of a deletion. v0.4.3 updates “END” coordinate in INFO field.
05/04/2020: Release version 0.4.2
Support GVCF file conversion.
03/24/2020: Release version 0.4.1
Fix the bug when there are consecutive TABs in the input MAF file.
10/09/2019: Release version 0.3.8
The University of California holds the copyrights in the UCSC chain files. As requested by UCSC, all UCSC generated chain files will be permanently removed from this website and the CrossMap distributions.
07/22/2019: Release version 0.3.6
Support MAF (mutation annotation format).
Fix error “TypeError: AlignmentHeader does not support item assignment (use header.to_dict()” when lifting over BAM files. User does not need to downgrade pysam to 0.13.0 to lift over BAM files.
04/01/2019: Release version 0.3.4
Fix bugs when chromosome IDs (of the source genome) in chain file do not have ‘chr’ prefix (such as “GRCh37ToHg19.over.chain.gz”). This version also allows CrossMap to detct if a VCF mapping was inverted, and if so reverse complements the altenerative allele (Thanks Andrew Yates). Improve wording.
01/07/2019: Release version 0.3.3
Version 0.3.3 is exactly the same as Version 0.3.2. The reason to release this version is that CrossMap-0.3.2.tar.gz was broken when uploading to pypi.
12/14/18: Release version 0.3.2
Fix the key error problem (e.g KeyError: “sequence ‘b‘7_KI270803v1_alt’’ not present”). This error happens when a locus from the orignal assembly is mapped to a “alternative”, “unplaced” or “unlocalized” contig in the target assembly, and this “target contig” does not exist in your target_ref.fa. In version 0.3.2, such loci will be silently skipped and saved to the “.unmap” file.
11/05/18: Release version 0.3.0
v0.3.0 or newer will Support Python3. Previous versions support Python2.7.*
add pyBigWig as a dependency.
Installation¶
pip3 install CrossMap #Install CrossMap supporting Python3
pip3 install CrossMap --upgrade #upgrade CrossMap supporting Python3
pip2 install CrossMap #Install CrossMap supporting Python2.7.*
pip2 install CrossMap --upgrade #upgrade CrossMap supporting Python2.7.*
Input and Output¶
Chain file¶
A chain file describes a pairwise alignment between two reference assemblies. UCSC and Ensemble chain files are available:
UCSC chain files
Chain files from hg38 (GRCh38) to hg19 and all other organisms: http://hgdownload.soe.ucsc.edu/goldenPath/hg38/liftOver/
Chain File from hg19 (GRCh37) to hg17/hg18/hg38 and all other organisms: http://hgdownload.soe.ucsc.edu/goldenPath/hg19/liftOver/
Chain File from mm10 (GRCm38) to mm9 and all other organisms: http://hgdownload.soe.ucsc.edu/goldenPath/mm10/liftOver/
Ensembl chain files
Human to Human: ftp://ftp.ensembl.org/pub/assembly_mapping/homo_sapiens/
Mouse to Mouse: ftp://ftp.ensembl.org/pub/assembly_mapping/mus_musculus/
Other organisms: ftp://ftp.ensembl.org/pub/assembly_mapping/
User Input file¶
CrossMap supports the following file formats.
Output file¶
The format of output files depends on the input
Input_format |
Output_format |
---|---|
BED |
BED (Genome coordinates will be updated) |
BAM |
BAM (Genome coordinates, header section, all SAM flags, insert size will be updated) |
CRAM |
BAM (require pysam >= 0.8.2) |
SAM |
SAM (Genome coordinates, header section, all SAM flags, insert size will be updated) |
Wiggle |
BigWig |
BigWig |
BigWig |
GFF |
GFF (Genome coordinates will be updated to the target assembly) |
GTF |
GTF (Genome coordinates will be updated to the target assembly) |
VCF |
VCF (header section, Genome coordinates, reference alleles will be updated) |
GVCF |
GVCF (header section, Genome coordinates, reference alleles will be updated) |
MAF |
MAF (Genome coordinates and reference alleles will be updated) |
Usage¶
Run CrossMap.py without any arguments will print help message
$CrossMap.py
Program: CrossMap (v0.4.3)
- Description:
CrossMap is a program to convert genome coordinates between different reference assemblies(e.g. from human hg19 to hg38 or vice versa). The supported file formats include BAM, BED, BigWig, CRAM, GFF, GTF, GVCF, MAF (mutation annotation format), SAM, Wiggle and VCF.
Usage: CrossMap.py <command> [options]
bam convert BAM, CRAM or SAM format file. bed convert BED, bedGraph or other BED-like file. bigwig convert BigWig file. gff convert GFF or GTF format file. gvcf convert GVCF file. maf convert MAF (mutation annotation format) file. region convert big genomic regions (in BED format) such as CNV blocks. vcf convert VCF file. wig convert Wiggle or bedGraph format file.
Convert BED format files¶
A BED (Browser Extensible Data) file is a tab-delimited text file describing genome regions or gene annotations. It consists of one line per feature, each containing 3-12 columns. CrossMap converts BED files with less than 12 columns to a different assembly by updating the chromosome and genome coordinates only; all other columns remain unchanged. Regions from old assembly mapping to multiple locations to the new assembly will be split. For 12-columns BED files, all columns will be updated accordingly except the 4th column (name of bed line), 5th column (score value) and 9th column (RGB value describing the display color). 12-column BED files usually define multiple blocks (e.g. exons); if any of the exons fails to map to a new assembly, the whole BED line is skipped.
The input BED file can be plain text file, compressed file with extension of .gz, .Z, .z, .bz, .bz2 and .bzip2, or even a URL pointing to accessible remote files (http://, https:// and ftp://). Compressed remote files are not supported. The output is a BED format file with exact the same number of columns as the original one.
Standard BED format has 12 columns, but CrossMap also supports BED-like formats:
BED3: The first 3 columns (“chrom”, “start”, “end”) of BED format file.
BED6: The first 6 columns (“chrom”, “start”, “end”, “name”, “score”, “strand”) of BED format file.
Other: Format has at least 3 columns (“chrom”, “start”, “end”) and no more than 12 columns. All other columns are arbitrary.
NOTE:
For BED-like formats mentioned above, CrossMap only updates “chrom (1st column)”, “start (2nd column) “, “end (3rd column) ” and “strand” (if any). All other columns will keep AS-IS.
Lines starting with ‘#’, ‘browser’, ‘track’ will be skipped.
Lines will less than 3 columns will be skipped.
2nd-column and 3-column must be integers, otherwise, the line will be skipped.
“+” strand is assumed if no strand information was found.
For standard BED format (12 columns). If any of the defined exon blocks cannot be uniquely mapped to target assembly, the whole entry will be skipped.
“input_chain_file” and “input_bed_file” can be regular or compressed (.gz, .Z, .z, .bz, .bz2, .bzip2) file, local file or URL (http://, https://, ftp://) pointing to remote file.
If output_file was not specified, results will be printed to screen (console). In this case, the original bed entries (include items failed to convert) were also printed out.
If input region cannot be consecutively mapped target assembly, it will be split.
*.unmap file contains regions that cannot be unambiguously converted.
Example run CrossMap with no output_file specified:
$ CrossMap.py bed hg18ToHg19.over.chain.gz test.hg18.bed3
# Conversion results were printed to screen directly (column1-3 are hg18 based, column5-7 are hg19 based)::
chr1 142614848 142617697 -> chr1 143903503 143906352
chr1 142617697 142623312 -> chr1 143906355 143911970
chr1 142623313 142623350 -> chr1 143911971 143912008
Example run CrossMap with output_file (test.hg19.bed3) specified:
$ CrossMap.py bed hg18ToHg19.over.chain.gz test.hg18.bed3 test.hg19.bed3
$ cat test.hg19.bed3
chr1 143903503 143906352
chr1 143906355 143911970
chr1 143911971 143912008
Example One input region was split because it cannot be consecutively mapped to the target assembly:
$ CrossMap.py bed hg18ToHg19.over.chain.gz test.hg18.bed3
chr10 81369946 81370453 + -> chr10 81380000 81380507 +
chr10 81370483 81371363 + -> chr10 81380539 81381419 +
chr10 81371363 81371365 + -> chr10 62961832 62961834 +
chr10 81371412 81371432 + (split.1:chr10:81371412:81371422:+) chr10 62961775 62961785 +
chr10 81371412 81371432 + (split.2:chr10:81371422:81371432:+) chrX 63278348 63278358 +
Example Use bed command to convert a bedGraph file, output another bedGraph file. Use wig command to convert a bedGraph file, output a bigWig file.:
$ CrossMap.py bed hg19ToHg38.over.chain.gz 4_hg19.bgr
chrX 5873316 5873391 2.0 -> chrX 5955275 5955350 2.0
chrX 5873673 5873710 0.8 -> chrX 5955632 5955669 0.8
chrX 5873710 5873785 1.4 -> chrX 5955669 5955744 1.4
chrX 5873896 5873929 0.9 -> chrX 5955855 5955888 0.9
chrX 5873929 5874004 1.5 -> chrX 5955888 5955963 1.5
chrX 5874230 5874471 0.3 -> chrX 5956189 5956430 0.3
chrX 5874471 5874518 0.9 -> chrX 5956430 5956477 0.9
$ python3 CrossMap.py wig hg19ToHg38.over.chain.gz 4_hg19.bgr output_hg38
@ 2018-11-06 00:09:11: Read chain_file: hg19ToHg38.over.chain.gz
@ 2018-11-06 00:09:12: Liftover wiggle file: 4_hg19.bgr ==> output_hg38.bgr
@ 2018-11-06 00:09:12: Merging overlapped entries in bedGraph file ...
@ 2018-11-06 00:09:12: Sorting bedGraph file:output_hg38.bgr
@ 2018-11-06 00:09:12: Writing header to "output_hg38.bw" ...
@ 2018-11-06 00:09:12: Writing entries to "output_hg38.bw" ...
Example Use region command to convert large genomic regions in BED format.
# a genomic region of 3.48Mb
$ cat test.bed
chr2 239716679 243199373
Using bed command to convert this 3.48Mb region. It will be split into 74 blocks:
$CrossMap.py bed GRCh37_to_GRCh38.chain.gz test.bed
chr2 239716679 243199373 (split.1:chr2:239716679:239801978:+) chr2 238808038 238893337
chr2 239716679 243199373 (split.2:chr2:239831978:240205681:+) chr2 238910282 239283985
chr2 239716679 243199373 (split.3:chr2:240205681:240319336:+) chr2 239283986 239397641
... (split 74 times)
Using region command to convert this 3.48Mb region. “-r” (the minimum ratio of bases that must remap) is 0.85 by default:
$CrossMap.py region GRCh37_to_GRCh38.chain.gz test.bed
chr2 239716679 243199373 -> chr2 238808038 242183529 map_ratio=0.9622
Increase -r to 0.99:
$CrossMap.py region GRCh37_to_GRCh38.chain.gz test.bed -r 0.99
chr2 239716679 243199373 Fail map_ratio=0.9622
Convert BAM/CRAM/SAM format files¶
SAM (Sequence Alignment Map) format is a generic format for storing sequencing alignments, and BAM is binary and compressed version of SAM (Li et al., 2009). CRAM was designed to be an efficient reference-based alternative to the SAM and BAM file formats Most high-throughput sequencing (HTS) alignments were in SAM/BAM format and many HTS analysis tools work with SAM/BAM format. CrossMap updates chromosomes, genome coordinates, header sections, and all SAM flags accordingly. CrossMap’s version number is inserted into the header section, along with the names of the original BAM file and the chain file. For pair-end sequencing, insert size is also recalculated. The input BAM file should be sorted and indexed properly using samTools (Li et al., 2009). Output format is determined from the input format and BAM output will be sorted and indexed automatically.
Typing command without any arguments will print help message:
Usage:
CrossMap.py bam <chain_file> <input.bam> [output_file] [options]
Note:
If output_file is 'STDOUT','-' or missing, CrossMap will write BAM file to the screen
Options:
-m INSERT_SIZE, --mean=INSERT_SIZE
Average insert size of pair-end sequencing (bp).
{default=200.0}
-s INSERT_SIZE_STDEV, --stdev=INSERT_SIZE_STDEV
Stanadard deviation of insert size. {default=30.0}
-t INSERT_SIZE_FOLD, --times=INSERT_SIZE_FOLD
A mapped pair is considered as "proper pair" if both
ends mapped to different strand and
the distance between them is less then '-t' * stdev
from the mean. {default=3.0}
-a, --append-tags Add tag to each alignment.
Example (Convert BAM from hg19 to hg18):
# add optional tags using '-a' (recommend always use '-a' option)
$ CrossMap.py bam -a ../data/hg19ToHg18.over.chain.gz test.hg19.bam test.hg18
Insert size = 200.000000
Insert size stdev = 30.000000
Number of stdev from the mean = 3.000000
Add tags to each alignment = True
@ 2016-10-07 15:29:06: Read chain_file: ../data/hg19ToHg18.over.chain.gz
@ 2016-10-07 15:29:07: Liftover BAM file: test.hg19.bam ==> test.hg18.bam
@ 2016-10-07 15:29:14: Done!
@ 2016-10-07 15:29:14: Sort "test.hg18.bam" ...
@ 2016-10-07 15:29:15: Index "test.hg18.sorted.bam" ...
Total alignments:99914
QC failed: 0
R1 unique, R2 unique (UU): 96094
R1 unique, R2 unmapp (UN): 3579
R1 unique, R2 multiple (UM): 0
R1 multiple, R2 multiple (MM): 0
R1 multiple, R2 unique (MU): 233
R1 multiple, R2 unmapped (MN): 8
R1 unmap, R2 unmap (NN): 0
R1 unmap, R2 unique (NU): 0
R1 unmap, R2 multiple (NM): 0
# BAM/SAM header sections was updated:
$ samtools view -H test.hg19.bam
@SQ SN:chr1 LN:249250621
@SQ SN:chr2 LN:243199373
@SQ SN:chr3 LN:198022430
...
@SQ SN:chrX LN:155270560
@SQ SN:chrY LN:59373566
@SQ SN:chrM LN:16571
@RG ID:Sample_618545BE SM:Sample_618545BE LB:Sample_618545BE PL:Illumina
@PG ID:bwa PN:bwa VN:0.6.2-r126
$ samtools view -H test.hg18.bam
@HD VN:1.0 SO:coordinate
@SQ SN:chr1 LN:247249719
@SQ SN:chr10 LN:135374737
@SQ SN:chr11 LN:134452384
...
@SQ SN:chrX LN:154913754
@SQ SN:chrX_random LN:1719168
@SQ SN:chrY LN:57772954
@RG ID:Sample_618545BE SM:Sample_618545BE LB:Sample_618545BE PL:Illumina
@PG PN:bwa ID:bwa VN:0.6.2-r126
@PG ID:CrossMap VN:0.5.0
@CO Liftover from original BAM/SAM file: test.hg19.bam
@CO Liftover is based on the chain file: ../test/hg19ToHg18.over.chain.gz
Optional tags:
- Q
QC. QC failed.
- N
Unmapped. Originally unmapped or originally mapped but failed to lift over to new assembly.
- M
Multiple mapped. Alignment can be lifted over to multiple places.
- U
Unique mapped. Alignment can be lifted over to only 1 place.
Tags for pair-end sequencing include:
QF = QC failed
NN = both read1 and read2 unmapped
NU = read1 unmapped, read2 unique mapped
NM = read1 unmapped, multiple mapped
UN = read1 uniquely mapped, read2 unmap
UU = both read1 and read2 uniquely mapped
UM = read1 uniquely mapped, read2 multiple mapped
MN = read1 multiple mapped, read2 unmapped
MU = read1 multiple mapped, read2 unique mapped
MM = both read1 and read2 multiple mapped
Tags for single-end sequencing include:
QF = QC failed
SN = unmaped
SM = multiple mapped
SU = uniquely mapped
Note
All alignments (mapped, partial mapped, unmapped, QC failed) will write to one file. Users can filter them by tags.
Header section will be updated to the target assembly.
Genome coordinates and all SAM flags in the alignment section will be updated to the target assembly.
If the input is a CRAM file, pysam version should >= 0.8.2
Optional fields in the alignment section will not update.
Convert Wiggle format files¶
Wiggle (WIG) format is useful for displaying continuous data such as GC content and the reads intensity of high-throughput sequencing data. BigWig is a self-indexed binary-format Wiggle file, and has the advantage of supporting random access. Input wiggle data can be in variableStep (for data with irregular intervals) or fixedStep (for data with regular intervals). Regardless of the input, the output files are always in bedGraph format. We export files in bedGraph format because it’s more compact than wiggle format, and more importantly, CrossMap internally transforms wiggle into bedGraph to increase running speed.
Typing command without any arguments will print help message:
$ CrossMap.py wig
Usage
-----
CrossMap.py wig <chain_file> <input.wig> <output_prefix>
Description
-----------
Convert wiggle format file. The "chain_file" can be regular or compressed (*.gz,
*.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL (http://, https://,
ftp://) pointing to remote file. Both "variableStep" and "fixedStep" wiggle
lines are supported. Wiggle format:
http://genome.ucsc.edu/goldenPath/help/wiggle.html
Example
-------
CrossMap.py wig hg18ToHg19.over.chain.gz test.hg18.wig test.hg19
Note
To improve performance, this script calls GNU “sort” command internally. If “sort” command does not exist, CrossMap will exit.
Convert BigWig format files¶
If an input file is in BigWig format, the output is BigWig format if UCSC’s ‘wigToBigWig’ executable can be found; otherwise, the output file will be in bedGraph format.
After v0.3.0, UCSC’s wigToBigWig is no longer needed.
Typing command without any arguments will print help message:
$ CrossMap.py bigwig
Usage
-----
CrossMap.py bigwig <chain_file> <input.bigwig> <output_prefix>
Description
-----------
Convert BigWig format file. The "chain_file" can be regular or compressed (*.gz,
*.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL (http://, https://,
ftp://) pointing to remote file. Bigwig format:
http://genome.ucsc.edu/goldenPath/help/bigWig.html
Example
-------
CrossMap.py bigwig hg18ToHg19.over.chain.gz test.hg18.bw test.hg19
Example (Convert BigWig file from hg18 to hg19):
$ python CrossMap.py bigwig hg19ToHg18.over.chain.gz test.hg19.bw test.hg18
@ 2013-11-17 22:12:42: Read chain_file: ../data/hg19ToHg18.over.chain.gz
@ 2013-11-17 22:12:44: Liftover bigwig file: test.hg19.bw ==> test.hg18.bgr
@ 2013-11-17 22:15:38: Merging overlapped entries in bedGraph file ...
@ 2013-11-17 22:15:38: Sorting bedGraph file:test.hg18.bgr
@ 2013-11-17 22:15:39: Convert wiggle to bigwig ...
Note
To improve performance, this script calls GNU “sort” command internally. If “sort” command does not exist, CrossMap will exit.
Convert GFF/GTF format files¶
GFF (General Feature Format) is another plain text file used to describe gene structure. GTF (Gene Transfer Format) is a refined version of GTF. The first eight fields are the same as GFF. Plain text, compressed plain text, and URLs pointing to remote files are all supported. Only chromosome and genome coordinates are updated. The format of the output is determined from the input.
Typing command without any arguments will print help message:
$ CrossMap.py gff
Usage
-----
CrossMap.py gff <chain_file> <input.gff> <output_file>
Description
-----------
Convert GFF or GTF format file. The"chain_file" can be regular or compressed
(*.gz, *.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL (http://,
https://, ftp://) pointing to remote file. Input file must be in GFF or GTF
format. GFF format: http://genome.ucsc.edu/FAQ/FAQformat.html#format3 GTF
format: http://genome.ucsc.edu/FAQ/FAQformat.html#format4
Example1 (write output to file)
-------------------------------
CrossMap.py gff hg19ToHg18.over.chain.gz test.hg19.gtf test.hg18.gtf
Example2 (write output to screen)
---------------------------------
CrossMap.py gff hg19ToHg18.over.chain.gz test.hg19.gtf
Example (Convert GTF file from hg19 to hg18):
$ python CrossMap.py gff hg19ToHg18.over.chain.gz test.hg19.gtf test.hg18.gtf
@ 2013-11-17 20:44:47: Read chain_file: ../data/hg19ToHg18.over.chain.gz
$ head test.hg19.gtf
chr1 hg19_refGene CDS 48267145 48267291 0.000000 - 0 gene_id "NM_001194986"; transcript_id "NM_001194986";
chr1 hg19_refGene exon 66081691 66081907 0.000000 + . gene_id "NM_002303"; transcript_id "NM_002303";
chr1 hg19_refGene CDS 145334684 145334792 0.000000 + 2 gene_id "NM_001039703"; transcript_id "NM_001039703";
chr1 hg19_refGene exon 172017752 172017890 0.000000 + . gene_id "NM_001136127"; transcript_id "NM_001136127";
chr1 hg19_refGene CDS 206589249 206589333 0.000000 + 2 gene_id "NM_001170637"; transcript_id "NM_001170637";
chr1 hg19_refGene exon 210573812 210574006 0.000000 + . gene_id "NM_001170580"; transcript_id "NM_001170580";
chr1 hg19_refGene CDS 235850249 235850347 0.000000 - 0 gene_id "NM_000081"; transcript_id "NM_000081";
chr1 hg19_refGene CDS 235880012 235880078 0.000000 - 1 gene_id "NM_000081"; transcript_id "NM_000081";
chr1 hg19_refGene exon 3417741 3417872 0.000000 - . gene_id "NM_001409"; transcript_id "NM_001409";
chr1 hg19_refGene exon 10190773 10190871 0.000000 + . gene_id "NM_006048"; transcript_id "NM_006048";
$ head test.hg18.gtf
chr1 hg19_refGene CDS 48039732 48039878 0.000000 - 0 gene_id "NM_001194986"; transcript_id "NM_001194986";
chr1 hg19_refGene exon 65854279 65854495 0.000000 + . gene_id "NM_002303"; transcript_id "NM_002303";
chr1 hg19_refGene CDS 144046041 144046149 0.000000 + 2 gene_id "NM_001039703"; transcript_id "NM_001039703";
chr1 hg19_refGene exon 170284375 170284513 0.000000 + . gene_id "NM_001136127"; transcript_id "NM_001136127";
chr1 hg19_refGene CDS 204655872 204655956 0.000000 + 2 gene_id "NM_001170637"; transcript_id "NM_001170637";
chr1 hg19_refGene exon 208640435 208640629 0.000000 + . gene_id "NM_001170580"; transcript_id "NM_001170580";
chr1 hg19_refGene CDS 233916872 233916970 0.000000 - 0 gene_id "NM_000081"; transcript_id "NM_000081";
chr1 hg19_refGene CDS 233946635 233946701 0.000000 - 1 gene_id "NM_000081"; transcript_id "NM_000081";
chr1 hg19_refGene exon 3407601 3407732 0.000000 - . gene_id "NM_001409"; transcript_id "NM_001409";
chr1 hg19_refGene exon 10113360 10113458 0.000000 + . gene_id "NM_006048"; transcript_id "NM_006048";
Note
Each feature (exon, intron, UTR, etc) is processed separately and independently, and we do NOT check if features originally belonging to the same gene were converted into the same gene.
If user wants to lift over gene annotation files, use BED12 format.
If no output file was specified, the output will be printed to screen (console). In this case, items failed to convert are also printed out.
Convert VCF format files¶
VCF (variant call format) is a flexible and extendable line-oriented text format developed by the 1000 Genome Project. It is useful for representing single nucleotide variants, indels, copy number variants, and structural variants. Chromosomes, coordinates, and reference alleles are updated to a new assembly, and all the other fields are not changed.
Typing command without any arguments will print help message:
$ CrossMap.py vcf
usage
-----
CrossMap.py vcf <chain_file> <input.vcf> <refGenome.fa> <output_file>
Description
-----------
Convert VCF format file. The "chain_file" and "input.vcf" can be regular or
compressed (*.gz, *.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL
(http://, https://, ftp://) pointing to remote file. "refGenome.fa" is genome
sequence file of the *target assembly*.
Example
-------
CrossMap.py vcf hg19ToHg18.over.chain.gz test.hg19.vcf hg18.fa test.hg18.vcf
Example (Convert VCF file from hg19 to hg18):
$ python CrossMap.py vcf hg19ToHg18.over.chain.gz test.hg19.vcf ../database/genome/hg18.fa test.hg18.vcf
@ 2015-07-27 10:14:23: Read chain_file: ../data/hg19ToHg18.over.chain.gz
@ 2013-11-17 20:53:39: Creating index for ../database/genome/hg18.fa
@ 2015-07-27 10:14:50: Total entries: 497
@ 2015-07-27 10:14:50: Failed to map: 0
$ grep -v '#' test.hg19.vcf |head -10
chr1 10933566 . C G . PASS ADP=13;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:7:13:13:0:13:100%:9.6148E-8:0:36:0:0:8:5
chr1 11187893 . T C . PASS ADP=224;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:133:226:224:0:224:100%:3.6518E-134:0:38:0:0:41:183
chr1 11205058 . C T . PASS ADP=625;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:255:643:625:0:625:100%:0E0:0:37:0:0:294:331
chr1 11292753 . A G . PASS ADP=52;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:27:52:52:2:50:96.15%:9.0394E-28:39:38:0:2:0:50
chr1 11318763 . C G . str10 ADP=88;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:51:88:88:0:88:100%:1.7384E-52:0:38:0:0:1:87
chr1 11319587 . A G . PASS ADP=70;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:40:70:70:0:70:100%:1.0659E-41:0:38:0:0:0:70
chr1 16202995 . C T . PASS ADP=463;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:463:463:458:5:1.08%:3.0913E-2:37:33:188:270:4:1
chr1 27088546 . A T . PASS ADP=124;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:21:124:124:65:59:47.58%:1.7915E-22:37:38:59:6:55:4
chr1 27101390 . T C . str10 ADP=267;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:267:267:262:5:1.87%:3.0665E-2:32:22:85:177:5:0
chr1 34007097 . T C . PASS ADP=10;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:10:10:6:4:40%:4.3344E-2:34:32:0:6:0:4
$ grep -v '#' test.hg18.vcf |head -10
1 10856153 . C G . PASS ADP=13;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:7:13:13:0:13:100%:9.6148E-8:0:36:0:0:8:5
1 11110480 . T C . PASS ADP=224;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:133:226:224:0:224:100%:3.6518E-134:0:38:0:0:41:183
1 11127645 . C T . PASS ADP=625;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:255:643:625:0:625:100%:0E0:0:37:0:0:294:331
1 11215340 . A G . PASS ADP=52;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:27:52:52:2:50:96.15%:9.0394E-28:39:38:0:2:0:50
1 11241350 . C G . str10 ADP=88;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:51:88:88:0:88:100%:1.7384E-52:0:38:0:0:1:87
1 11242174 . A G . PASS ADP=70;WT=0;HET=0;HOM=1;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 1/1:40:70:70:0:70:100%:1.0659E-41:0:38:0:0:0:70
1 16075582 . C T . PASS ADP=463;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:463:463:458:5:1.08%:3.0913E-2:37:33:188:270:4:1
1 26961133 . A T . PASS ADP=124;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:21:124:124:65:59:47.58%:1.7915E-22:37:38:59:6:55:4
1 26973977 . T C . str10 ADP=267;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:267:267:262:5:1.87%:3.0665E-2:32:22:85:177:5:0
1 33779684 . T C . PASS ADP=10;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:10:10:6:4:40%:4.3344E-2:34:32:0:6:0:4
$ grep -v '#' test.hg18.vcf.unmap #coordinates are still based on hg19
chr14 20084444 . G C . PASS ADP=253;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:1:253:253:247:5:1.98%:3.0631E-2:38:39:123:124:5:0
chr14 20086290 . T C . PASS ADP=441;WT=0;HET=1;HOM=0;NC=0 GT:GQ:SDP:DP:RD:AD:FREQ:PVAL:RBQ:ABQ:RDF:RDR:ADF:ADR 0/1:4:441:441:427:14:3.17%:5.4963E-5:37:38:236:191:6:8
Note
Genome coordinates and reference allele will be updated to target assembly.
Reference genome is genome sequence of target assembly.
If the reference genome sequence file (../database/genome/hg18.fa) was not indexed, CrossMap will automatically indexed it (only the first time you run CrossMap).
Output files: output_file and output_file.unmap.
In the output VCF file, whether the chromosome IDs contain “chr” or not depends on the format of the input VCF file.
Interpretation of Failed tags:
Fail(Multiple_hits) : This genomic location were mapped to two or more locations to the target assembly.
Fail(REF==ALT) : After liftover, the reference allele and the alternative allele are same (i.e. this is NOT an SNP/variant after liftover)
Fail(Unmap) : Unable to map this genomic location to the target assembly.
Fail(KeyError) : Unable to find the contig ID (or chromosome ID) from the reference genome sequence (of the target assembly).
Convert MAF format files¶
MAF (mutation annotation format) files are tab-delimited files that contain somatic and/or germline mutation annotations. Please do not confused with Multiple Alignment Format.
Typing command without any arguments will print help message:
$ CrossMap.py maf
usage
-----
CrossMap.py maf <chain_file> <input.maf> <refGenome.fa> <build_name>
<output_file>
Description
-----------
Convert MAF format file. The "chain_file" and "input.maf" can be regular or
compressed (*.gz, *.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL
(http://, https://, ftp://) pointing to remote file. "refGenome.fa" is genome
sequence file of *target assembly*. "build_name" is the name of the
*target_assembly* (eg "GRCh38")
Example
-------
CrossMap.py maf hg19ToHg38.over.chain.gz test.hg19.maf hg38.fa GRCh38 test.hg38.maf
Convert GVCF format files¶
Typing command without any arguments will print help message:
$ CrossMap.py gvcf
usage
-----
CrossMap.py gvcf <chain_file> <input.gvcf> <refGenome.fa> <output_file>
Description
-----------
Convert GVCF format file. The "chain_file" and "input.gvcf" can be regular or
compressed (*.gz, *.Z, *.z, *.bz, *.bz2, *.bzip2) file, local file or URL
(http://, https://, ftp://) pointing to remote file. "refGenome.fa" is genome
sequence file of the *target assembly*.
Example
-------
CrossMap.py gvcf hg19ToHg18.over.chain.gz test.hg19.gvcf hg18.fa test.hg18.gvcf
Example (Convert GVCF file from hg19 to hg38):
$ CrossMap.py gvcf GRCh37_to_GRCh38.chain.gz test.hg19.gvcf Homo_sapiens.GRCh38.dna.primary_assembly.fa test.hg38.gvcf
@ 2020-05-04 13:17:23: Read the chain file: ../CrossMap-0.2.9.git/data/human/GRCh37_to_GRCh38.chain.gz
@ 2020-05-04 13:17:23: Updating contig field ...
@ 2020-05-04 13:17:23: Lifting over ...
@ 2020-05-04 13:17:23: Total variants: 9
@ 2020-05-04 13:17:23: Variants failed to map: 0
@ 2020-05-04 13:17:23: Total non-variant regions: 22
@ 2020-05-04 13:17:23: Non-variant regions failed to map: 0
Convert large genomic regions¶
For large genomic regions such as CNV blocks, the CrossMap.py bed
will split each large region into smaller blocks that are 100% matched to the target assembly.
CrossMap.py target
will NOT split large regions, instead, it will calculate the map ratio (i.e. {bases mapped to target genome} / {total bases in query region}). If the
map ratio is larger than the threshold specified by -r
, the coordinates will be converted to the target genome, otherwise, fails.
Typing command without any arguments will print help message:
Usage
-----
CrossMap.py region <chain_file> <regions.bed> [output_file] [options]
Examples:
CrossMap.py region hg18ToHg19.over.chain.gz CNV.hg18.bed CNV.hg19.bed # write to file
CrossMap.py region hg18ToHg19.over.chain.gz CNV.hg18.bed # write to screen
Options:
-r MIN_MAP_RATIO, --ratio=MIN_MAP_RATIO
Minimum ratio of bases that must remap. {default=0.85}
Example:
$CrossMap.py region GRCh37_to_GRCh38.chain.gz test11_hg19_region.bed
@ 2020-08-14 16:46:04: Read the chain file: ../data/human/GRCh37_to_GRCh38.chain.gz
chr1 0 2500000 -> chr1 10000 2568561 map_ratio=0.9360
chr1 145394955 145807817 -> chr1 145627235 146040039 map_ratio=0.9994
chr1 146527987 147394444 -> chr1 147056425 147922330 map_ratio=0.9989
chr10 82045472 88931651 -> chr10 80285716 87171894 map_ratio=1.0000
chr11 43940000 46020000 -> chr11 43918450 45998449 map_ratio=1.0000
chr15 22805313 23094530 Fail map_ratio=0.3607
chr15 22805313 28390339 -> chr15 22598414 28145193 map_ratio=0.8967
chr15 31080645 32462776 -> chr15 30788442 32170575 map_ratio=1.0000
chr15 72900171 78151253 -> chr15 72607830 77858911 map_ratio=1.0000
chr15 83219735 85722039 -> chr15 82550985 85178808 map_ratio=0.9800
chr16 15511655 16293689 -> chr16 15417798 16199832 map_ratio=1.0000
chr16 21950135 22431889 -> chr16 21938814 22420568 map_ratio=1.0000
chr16 28823196 29046783 -> chr16 28811875 29035462 map_ratio=1.0000
chr16 29650840 30200773 -> chr16 29639519 30189452 map_ratio=1.0000
chr17 1247834 1303556 -> chr17 1344540 1400262 map_ratio=1.0000
chr17 2496923 2588909 -> chr17 2593629 2685615 map_ratio=1.0000
chr17 16812771 20211017 -> chr17 16909457 20307704 map_ratio=1.0000
chr17 29107491 30265075 -> chr17 30780473 31938056 map_ratio=1.0000
chr17 34815904 36217432 Unmap
chr17 43705356 44164691 -> chr17 45627990 46087325 map_ratio=1.0000
chr2 50145643 51259674 -> chr2 49918505 51032536 map_ratio=1.0000
chr2 96742409 97677516 -> chr2 96076661 97011779 map_ratio=1.0000
chr2 111394040 112012649 -> chr2 110636463 111255072 map_ratio=1.0000
chr2 239716679 243199373 -> chr2 238808038 242183529 map_ratio=0.9622
chr22 19037332 21466726 Fail map_ratio=0.8490
chr22 21920127 23653646 -> chr22 21565838 23311459 map_ratio=0.9996
chr22 51113070 51171640 -> chr22 50674642 50733212 map_ratio=1.0000
chr3 195720167 197354826 -> chr3 195993296 197627955 map_ratio=1.0000
chr4 1552030 2091303 -> chr4 1550303 2089576 map_ratio=1.0000
chr5 175720924 177052594 -> chr5 176293921 177625593 map_ratio=1.0000
chr7 72744915 74142892 -> chr7 73330912 74728554 map_ratio=0.9997
chr8 8098990 11872558 -> chr8 8241468 12015049 map_ratio=1.0000
chr9 140513444 140730578 -> chr9 137618992 137836126 map_ratio=1.0000
Compare to UCSC liftover tool¶
To access the accuracy of CrossMap, we randomly generated 10,000 genome intervals (download from here) with the fixed interval size of 200 bp from hg19. Then we converted them into hg18 using CrossMap and UCSC liftover tool with default configurations. We compare CrossMap to UCSC liftover tool because it is the most widely used tool to convert genome coordinates.
CrossMap failed to convert 613 intervals, and UCSC liftover tool failed to convert 614 intervals. All failed intervals are exactly the same except one region (chr2 90542908 90543108). UCSC failed to convert it because this region needs to be split twice:
Original (hg19) |
Split (hg19) |
Target (hg18) |
---|---|---|
chr2 90542908 90543108 - |
chr2 90542908 90542933 - |
chr2 89906445 89906470 - |
chr2 90542908 90543108 - |
chr2 90542933 90543001 - |
chr2 87414583 87414651 - |
chr2 90542908 90543108 - |
chr2 90543010 90543108 - |
chr2 87414276 87414374 - |
For genome intervals that were successfully converted to hg18, the start and end coordinates are exactly the same between UCSC conversion and CrossMap conversion.

Citation¶
LICENSE¶
CrossMap is distributed under GNU General Public License
This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 2 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA
Contact¶
Wang.Liguo AT mayo.edu