Answers.Body: <p>A structural variant is an inversion, deletion, duplication, or translocation. A &quot;breakend&quot; is one endpoint of a structural variant. This paper (Alkan et al.  <em>Nature Review Genetics</em> 2011) may help you understand: <a href="https://www.nature.com/articles/nrg2958" rel="nofollow noreferrer">https://www.nature.com/articles/nrg2958</a></p>
  <p>The Manta paper and documentation seem sparse on diagrams. DELLY, another structural variant caller, has diagrams in their publication. Their paper may be more of use: <a href="https://academic.oup.com/bioinformatics/article/28/18/i333/245403" rel="nofollow noreferrer">https://academic.oup.com/bioinformatics/article/28/18/i333/245403</a></p>
  <p><strong>Specific example:</strong> Say you're sequencing a chronic myeloid leukemia (CML) tumor. You will likely find reads that half map to the ABL1 gene on chr9 and half map to the BCR gene on chr22 (<a href="https://en.wikipedia.org/wiki/Philadelphia_chromosome" rel="nofollow noreferrer">https://en.wikipedia.org/wiki/Philadelphia_chromosome</a>). The genomic position of the location where chr9 turns to chr22 is called the breakpoint. The positions on chr9 and chr22 are the breakends.</p>
  
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Answers.Text: Is it correct to say that the *breakpoint* is always on the sequence that I'm aligning to the reference, while the *breakends* always refer to the genomic positions in the reference genome?
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Answers.Text: I'd say breakpoint and breakends both refer to the genomic positions in the reference genome. A breakpoint typically contains two breakends, one for each genomic position.
  
  The sequences you're aligning to the reference would be called "supporting reads". They could be split (half aligns to one position, half to another), or paired-end reads (one read maps to one position, its mate pair to another).
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Answers.Body: <p>I think the term &quot;breakend&quot; is derived specifically from the VCF file spec:</p>
  <p><a href="https://samtools.github.io/hts-specs/VCFv4.2.pdf" rel="nofollow noreferrer">https://samtools.github.io/hts-specs/VCFv4.2.pdf</a></p>
  <p>Starting on page 12:</p>
  <p>&quot;5.4 Specifying complex rearrangements with breakends</p>
  <p>An arbitrary rearrangement event can be summarized as a set of novel adjacencies. Each adjacency ties together 2 breakends. The two breakends at either end of a novel adjacency are called mates.</p>
  <p>There is one line of VCF (i.e. one record) for each of the two breakends in a novel adjacency. A breakend record is identified with the tag “SVTYPE=BND” in the INFO field. The REF field of a breakend record indicates a base or
  sequence s of bases beginning at position POS, as in all VCF records. The ALT field of a breakend record indicates a replacement for s. This “breakend replacement” has three parts:</p>
  <ol>
  <li><p>The string t that replaces places s. The string t may be an extended version of s if some novel bases are inserted during the formation of the novel adjacency.</p>
  </li>
  <li><p>The position p of the mate breakend, indicated by a string of the form “chr:pos”. This is the location of the first mapped base in the piece being joined at this novel adjacency.</p>
  </li>
  <li><p>The direction that the joined sequence continues in, starting from p. This is indicated by the orientation of square brackets surrounding p. These 3 elements are combined in 4 possible ways to create the ALT. In each of the 4 cases, the assertion is that s is replaced with t, and then some piece starting at position p is joined to t. The cases are:</p>
  </li>
  </ol>
  <p>REF ALT Meaning</p>
  <p>s t[p[ piece extending to the right of p is joined after t</p>
  <p>s t]p] reverse comp piece extending left of p is joined after t</p>
  <p>s ]p]t piece extending to the left of p is joined before t</p>
  <p>s [p[t reverse comp piece extending right of p is joined before t</p>
  <p>The example in Figure 1 shows a 3-break operation involving 6 breakends. It exemplifies all possible orientations of breakends in adjacencies. Notice how the ALT field expresses the orientation of the breakends.</p>
  <p>#CHROM POS ID REF ALT QUAL FILTER INFO</p>
  <p>2 321681 bnd W G G]17:198982] 6 PASS SVTYPE=BND</p>
  <p>2 321682 bnd V T ]13:123456]T 6 PASS SVTYPE=BND</p>
  <p>13 123456 bnd U C C[2:321682[ 6 PASS SVTYPE=BND</p>
  <p>13 123457 bnd X A [17:198983[A 6 PASS SVTYPE=BND</p>
  <p>17 198982 bnd Y A A]2:321681] 6 PASS SVTYPE=BND</p>
  <p>17 198983 bnd Z C [13:123457[C 6 PASS SVTYPE=BND&quot;</p>
  
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Body: <p>I'm reading the Manta <a href="https://github.com/Illumina/manta/blob/master/docs/userGuide/README.md" rel="nofollow noreferrer">User Guide</a>
  → it is a method to discover structural variants and indels from next generation sequencing data.</p>
  <p>The word 'breakend' is used in several contexts</p>
  <p>I have searched for a definition in <code>duckduckgo</code>, <code>qwant</code> and <code>google</code> but have not found a concise definition.</p>
  <p>Thanks for you help</p>
  
Tags: <structural-variation>
Title: What is the exact definition of "breakend"?
ThreadText: # What is the exact definition of "breakend"?
  
  (Asked by: username_0 on 2021-03-22)
  
  I'm reading the Manta [User Guide](https://github.com/Illumina/manta/blob/master/docs/userGuide/README.md)
  → it is a method to discover structural variants and indels from next generation sequencing data.
  
  The word 'breakend' is used in several contexts
  
  I have searched for a definition in `duckduckgo`, `qwant` and `google` but have not found a concise definition.
  
  Thanks for you help
  
  **Tags:** structural-variation
  
  
  ---
  
  ## 2 answers
  
  ### Answer by username_1 on 2021-03-29. Score: 3 | Accepted answer
  
  A structural variant is an inversion, deletion, duplication, or translocation. A "breakend" is one endpoint of a structural variant. This paper (Alkan et al. *Nature Review Genetics* 2011) may help you understand: <https://www.nature.com/articles/nrg2958>
  
  The Manta paper and documentation seem sparse on diagrams. DELLY, another structural variant caller, has diagrams in their publication. Their paper may be more of use: <https://academic.oup.com/bioinformatics/article/28/18/i333/245403>
  
  **Specific example:** Say you're sequencing a chronic myeloid leukemia (CML) tumor. You will likely find reads that half map to the ABL1 gene on chr9 and half map to the BCR gene on chr22 (<https://en.wikipedia.org/wiki/Philadelphia_chromosome>). The genomic position of the location where chr9 turns to chr22 is called the breakpoint. The positions on chr9 and chr22 are the breakends.
  
  > **Comments:**
  > **username_0**: Is it correct to say that the *breakpoint* is always on the sequence that I'm aligning to the reference, while the *breakends* always refer to the genomic positions in the reference genome?  
  > **username_1**: I'd say breakpoint and breakends both refer to the genomic positions in the reference genome. A breakpoint typically contains two breakends, one for each genomic position.  The sequences you're aligning to the reference would be called "supporting reads". They could be split (half aligns to one position, half to another), or paired-end reads (one read maps to one position, its mate pair to another).  
  
  ---
  
  ### Answer by username_2 on 2023-11-08. Score: 2
  
  I think the term "breakend" is derived specifically from the VCF file spec:
  
  <https://samtools.github.io/hts-specs/VCFv4.2.pdf>
  
  Starting on page 12:
  
  "5.4 Specifying complex rearrangements with breakends
  
  An arbitrary rearrangement event can be summarized as a set of novel adjacencies. Each adjacency ties together 2 breakends. The two breakends at either end of a novel adjacency are called mates.
  
  There is one line of VCF (i.e. one record) for each of the two breakends in a novel adjacency. A breakend record is identified with the tag “SVTYPE=BND” in the INFO field. The REF field of a breakend record indicates a base or
  sequence s of bases beginning at position POS, as in all VCF records. The ALT field of a breakend record indicates a replacement for s. This “breakend replacement” has three parts:
  
  1. The string t that replaces places s. The string t may be an extended version of s if some novel bases are inserted during the formation of the novel adjacency.
  2. The position p of the mate breakend, indicated by a string of the form “chr:pos”. This is the location of the first mapped base in the piece being joined at this novel adjacency.
  3. The direction that the joined sequence continues in, starting from p. This is indicated by the orientation of square brackets surrounding p. These 3 elements are combined in 4 possible ways to create the ALT. In each of the 4 cases, the assertion is that s is replaced with t, and then some piece starting at position p is joined to t. The cases are:
  
  REF ALT Meaning
  
  s t[p[ piece extending to the right of p is joined after t
  
  s t]p] reverse comp piece extending left of p is joined after t
  
  s ]p]t piece extending to the left of p is joined before t
  
  s [p[t reverse comp piece extending right of p is joined before t
  
  The example in Figure 1 shows a 3-break operation involving 6 breakends. It exemplifies all possible orientations of breakends in adjacencies. Notice how the ALT field expresses the orientation of the breakends.
  
  #CHROM POS ID REF ALT QUAL FILTER INFO
  
  2 321681 bnd W G G]17:198982] 6 PASS SVTYPE=BND
  
  2 321682 bnd V T ]13:123456]T 6 PASS SVTYPE=BND
  
  13 123456 bnd U C C[2:321682[ 6 PASS SVTYPE=BND
  
  13 123457 bnd X A [17:198983[A 6 PASS SVTYPE=BND
  
  17 198982 bnd Y A A]2:321681] 6 PASS SVTYPE=BND
  
  17 198983 bnd Z C [13:123457[C 6 PASS SVTYPE=BND"
  
  
  ---
  
  