Cassis: Detection of genomic rearrangement breakpoints

Using Cassis with synteny blocks from Compara database

1 - Input data

     To execute this comparison, we obtained all necessary information from the Ensembl Genome Brower site (Build 57).

     The Build 57 was released in March 3rd, 2010 and contains information about the Homo sapiens assembly GRCh37 (released in February 2009) and about the Mus musculus assembly NCBI m37 (released in April 2007).

  1. FASTA sequences

    The FASTA sequences of the chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and X of the Homo sapiens and of the chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and X of the Mus musculus were downloaded from the Ensembl FTP site:


    We downloaded the FASTA files which contains the chromosome sequences after being processed by RepeatMasker (dna_rm).
    All files are renamed according to the pattern: [chromosome_name].fasta (Example: 1.fasta, 2.fasta, X.fasta, etc.)

  2. Orthologous synteny blocks

    We downloaded some mysql table dumps of the Compara database (dnafrag.onlychromosome.txt, dnafrag_region.txt and, synteny_region.txt) and we processed these files to obtain the list of orthologous synteny blocks.
    Download the list of orthologous synteny blocks


2 - Results

     The Compara database has 345 orthologous synteny blocks identified in the genomes of Homo sapiens and Mus musculus. Table 1 shows the minimum, maximum, mean and median length of these blocks.

Table 1: Homo sapiens and Mus musculus synteny blocks extracted from the Ensembl's Compara database
Description N Homo sapiens [length in bp] Mus musculus [length in bp]
Min Max Mean Median Min Max Mean Median
Compara database 345 108,946 58,118,452 7,844,447 3,697,691 102,552 52,624,330 7,077,399 3,172,511

     By processing these synteny blocks, Cassis identified 292 breakpoints. A total of 234 breakpoints can be processed by the segmentation process while the remaining 58 cannot because they do not meet the minimum length of 50,000 bp (caused by synteny block overlapping). Table 2 shows the distribution of the 292 identified breakpoints according to their classification.

Table 2: Distribution of the 292 identified breakpoints according to their classification
Description Status Number of breakpoints
Sequences SR, SA and, SB have their lengths bigger than the minimum limit. 1 234
Sequence SA is smaller than the allowed limit. -3 27
Sequence SB is smaller than the allowed limit. -4 22
Sequences SA and SB are smaller than the allowed limit. -5 9

     The 234 breakpoints which have sequences SR, SA and, SB with length bigger than or equal to 50,000 bp were processed by the segmentation step. Table 3 shows the minimum, maximum, mean and median breakpoint length before and after the segmentation process. It also shows the number of breakpoints which received status 1, 0 or, -1 (passed (1) or failed (0) in the statistical test that evaluates the significance of the segmentation or had no hits (-1) on the alignments of the sequences SR against SA and SR against SB).

Table 3: Minimum, maximum, mean and median breakpoint length before and after the segmentation
Description N Before segmentation [length in bp] After segmentation [length in bp]
Min Max Mean Median Min Max Mean Median
All breakpoints 234 1 15,172,525 463,422 114,679 21 4,238,335 163,619 65,865
Status = 1 207 1 15,172,525 503,025 124,520 21 4,238,335 164,782 53,257
Status = 0 26 1,386 521,357 160,279 77,096 14,773 532,964 154,983 100,582
Status = -1 1 147,243 147,243 147,243 147,243 147,243 147,243 147,243 147,243

     Of the 234 breakpoints which were classified with status 1, a total of 83 breakpoints had their length increased after the segmentation. Table 4 shows the minimum, maximum, mean and median length of these breakpoints, before and after the segmentation process.

Table 4: Minimum, maximum, mean and median length of the 83 breakpoints which had their length increased after the segmentation
Description N Before segmentation [length in bp] After segmentation [length in bp]
Min Max Mean Median Min Max Mean Median
Length (after) ≥ Length (before) 83 1 543,101 70,602 24,923 21 543,249 77,229 33,298

     A total of 124 breakpoints were classified with status 1 and had their length decreased after the segmentation process. Table 5 shows the minimum, maximum, mean and median length of these breakpoints, before and after the segmentation process.

Table 5: Minimum, maximum, mean and median length of the 124 breakpoints which had their length decreased after the segmentation
Description N Before segmentation [length in bp] After segmentation [length in bp] Length reduction [%]
Min Max Mean Median Min Max Mean Median Min Max Mean Median
Length (after) < Length (before) 124 848 15,172,525 792,470 251,879 174 4,238,335 223,386 73,567 0.25 99.86 57.30 61.32

     Figure 1 shows the histogram of the differences of the breakpoint lengths, before and after the segmentation step, for the 202 breakpoints which were classified with status 1.

Figure 1: Histogram of the breakpoint size differences between "before" and "after" the refinement step of Cassis applied to Ensembl synteny blocs.
(5 values larger than 5 Mbp have been removed for the purpose of readability)

3 - Download