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update parsing docs: mention local aligners
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golobor committed Mar 21, 2024
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Expand Up @@ -287,12 +287,17 @@ Note that "-" in the pair type means that pair is separated by unsequenced gap,
Aligner settings
-----------------

Aligning Hi-C reads often requires adjusting aligner settings.
We recommended using local DNA sequence aligners, such as `BWA-MEM <http://bio-bwa.sourceforge.net/>`_ and `Bowtie2 <http://bowtie-bio.sourceforge.net/bowtie2/index.shtml>`_ (in the local alignment mode),
as opposed to global aligners (e.g. Bowtie2 in the end-to-end mode).
Local aligners assume that DNA molecules may contain fragments aligning to different locations in the genome and thus are better suited for mapping chimeric Hi-C molecules.

Aligning Hi-C reads may further require adjusting aligner settings.
Some aligners assume DNA libraries contain only contiguous fragments, leading to 'mate rescue' where one read's alignment is modified or even forced based on its pair's alignment.
This behavior is incompatible with Hi-C, which produces chimeric molecules with unrelated alignments on each side.
To avoid erroneous results, disable mate rescue/pairing and align reads pairs independently.
In `bwa mem`, use the '-SP' flags to achieve this.


.. [1] Following the lead of `C-walks <https://www.nature.com/articles/nature20158>`_
.. [2] This procedure was first introduced in `HiC-Pro <https://github.com/nservant/HiC-Pro>`_
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