Hello Alexander,

Please see this previously answered mailing list question, "How does LiftOver 
Work?":

https://lists.soe.ucsc.edu/pipermail/genome/2008-March/015810.html

Hopefully this should answer some of your questions. If you still require 
assistance, please write back to us.

Kayla Smith
UCSC Genome Bioinformatics Group

----- "Alexander Stark" <[email protected]> wrote:

> Hi all,
> 
> we're using liftOver quite extensively to translate coordinates  
> between different species. In general, it seems to work quite well for
>  
> us and the results typically make sense when we inspect them visually.
>  
> However, sometimes we run into problems, especially for coordinate- 
> conversions between more distantly related species. Unfortunately, we 
> 
> could not find a more detailed description of how liftOver works  
> (apart from the short help it prints) and what the command line  
> parameters do - we hope someone can help.
> 
> It is our understanding that liftOver essentially uses the UCSC  
> alignments (or the underlying data) for the conversions. This should 
> 
> mean that any input region can map to 0, 1, or several contiguous  
> regions in the target genome, that the region length can change, and 
> 
> that only a certain fraction of the input nucleotides correspond to  
> (i.e. map to) target nucleotides.
> 
> We assume that the behavior of liftOver with respect to these can be 
> 
> controlled using the following parameters:
> 
> -minMatch=0.N Minimum ratio of bases that must remap. Default 0.95
> -minBlocks=0.N        Minimum ratio of alignment blocks/exons that must map 
> 
> (default 1.00)
> -fudgeThick           If thickStart/thickEnd is not mapped, use the closest  
> mapped base.  Recommended if using -minBlocks.
> -multiple               Allow multiple output regions
> -minChainT, -minChainQ  Minimum chain size in target/query, when  
> mapping to multiple output regions (default 0, 0)
> 
> Could you please give some details on what exactly the parameters do? 
> 
> This is very important for us to know in order to use the tool  
> appropriately. For example:
> 
> 1. What does "remap" mean for the minMatch parameter?
> Is it the fraction of input bases that have a target counterpart, i.e.
>  
> that would appear aligned in a sequence alignment (or is it the  
> fraction of target-bases that have an input counterpart)?
> 
> When relaxing this parameter, we typically get more lifted regions.  
> Are these however still orthologous/unique or will we run into a  
> specificity problem? I understand that liftOver only uses a pre- 
> computed alignment (or coordinate lookup-table) that - in principle - 
> 
> only contains alignments between orthologous regions. In other words, 
> 
> I do NOT expect liftOver to simply find more and more "matches" that 
> 
> make less and less sense as e.g. blast would do when lowering its  
> specificity.
> 
> 2. How does the minMatch parameter influence the growing & shrinking 
> 
> of region-length
> Does a more relaxed minMatch parameter allow for more variable region-
> 
> length between input and target regions? In other words: if it only  
> assesses the fraction of input nucleotides that have a counterpart,  
> the region can grow freely but not shrink and vice versa.
> 
> 3. Will we "loose" regions?
> When lowering minMatch, will regions that are uniquely mapped with a 
> 
> stringent minMatch parameter map to multiple regions/blocks and thus 
> 
> become unmapped?
> 
> 4. Does "multiple" allow that an input region spans multiple output  
> blocks or does it allow non-unique mapping (of the same region)
> 
> 5. What does minChainT and minChainQ mean (i.e. what is a chain size, 
> 
> etc.)?
> 
> 6. what does minBlocks do? does it apply to regions that span multiple
>  
> alignment blocks and require that the same number of alignment blocks 
> 
> must be in the input and target region?
> 
> Very many thanks for your help in advance and sorry for all the  
> questions.
> 
> Best,
> 
> Alex
> 
> 
> 
> 
> 
> **********
> Alexander Stark, PhD
> Group Leader
> Institute of Molecular Pathology (IMP)
> Dr. Bohr-Gasse 7; 1030 Vienna
> Austria
> 
> Tel. +43 (1) 79730-3380
> [email protected]
> http://www.imp.ac.at/research/alexander-stark/
> 
> 
> _______________________________________________
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> https://lists.soe.ucsc.edu/mailman/listinfo/genome
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