{"action":"created","issue":{"url":"https://api.github.com/repos/alexdobin/STAR/issues/39","labels_url":"https://api.github.com/repos/alexdobin/STAR/issues/39/labels{/name}","comments_url":"https://api.github.com/repos/alexdobin/STAR/issues/39/comments","events_url":"https://api.github.com/repos/alexdobin/STAR/issues/39/events","html_url":"https://github.com/alexdobin/STAR/issues/39","id":74375482,"number":39,"title":"Supporting GRCh38/hg38","user":{"login":"schelhorn","id":5024959,"avatar_url":"https://avatars.githubusercontent.com/u/5024959?v=3","gravatar_id":"","url":"https://api.github.com/users/schelhorn","html_url":"https://github.com/schelhorn","followers_url":"https://api.github.com/users/schelhorn/followers","following_url":"https://api.github.com/users/schelhorn/following{/other_user}","gists_url":"https://api.github.com/users/schelhorn/gists{/gist_id}","starred_url":"https://api.github.com/users/schelhorn/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/schelhorn/subscriptions","organizations_url":"https://api.github.com/users/schelhorn/orgs","repos_url":"https://api.github.com/users/schelhorn/repos","events_url":"https://api.github.com/users/schelhorn/events{/privacy}","received_events_url":"https://api.github.com/users/schelhorn/received_events","type":"User","site_admin":false},"labels":[],"state":"open","locked":false,"assignee":null,"milestone":null,"comments":5,"created_at":"2015-05-08T14:10:17Z","updated_at":"2015-05-12T09:40:18Z","closed_at":null,"body":"I was wondering how STAR development will continue with regard to the new GRCh38/hg38 assembly and the existence of ALT contigs ([Reference 1](https://www.biostars.org/p/59126/) [Reference 2](http://www.bio-itworld.com/2013/4/22/church-on-reference-genomes-past-present-future.html)). To quote Heng Li:\r\n\r\n> GRCh38 ALT contigs are totaled 109Mb in length, spanning 60Mbp of the primary assembly. However, sequences that are highly diverged from the primary assembly only contribute a few million bp. Most subsequences of ALT contigs are nearly identical to the primary assembly. If we align sequence reads to GRCh38+ALT blindly, we will get many additional reads with zero mapping quality and miss variants on them. It is crucial to make mappers aware of ALTs. [Source](https://github.com/lh3/bwa/blob/master/README-alt.md)\r\n\r\nHeng developed [bwakit]( https://github.com/lh3/bwa/tree/master/bwakit) to approach a solution to ALT mapping for DNA-Seq, but as far as I know no similar implementation for RNA-Seq/spliced mapping has been proposed as of now. Since all relevant genome annotations for GRCh38/hg38 have been published, how is the recommended workflow for STAR concerning the new assembly? \r\n\r\nObviously, one can just remove the ALT contigs and map against hg38-noalt, but that would disregard the interesting advantages of the ALTs. Also, future assemblies will continue to capture known variation (until we will use the string graph directly, I imagine), so I suggest it could be fruitful sense to think about the consequences of this new assembly structure for spliced read mapping."},"comment":{"url":"https://api.github.com/repos/alexdobin/STAR/issues/comments/101214342","html_url":"https://github.com/alexdobin/STAR/issues/39#issuecomment-101214342","issue_url":"https://api.github.com/repos/alexdobin/STAR/issues/39","id":101214342,"user":{"login":"schelhorn","id":5024959,"avatar_url":"https://avatars.githubusercontent.com/u/5024959?v=3","gravatar_id":"","url":"https://api.github.com/users/schelhorn","html_url":"https://github.com/schelhorn","followers_url":"https://api.github.com/users/schelhorn/followers","following_url":"https://api.github.com/users/schelhorn/following{/other_user}","gists_url":"https://api.github.com/users/schelhorn/gists{/gist_id}","starred_url":"https://api.github.com/users/schelhorn/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/schelhorn/subscriptions","organizations_url":"https://api.github.com/users/schelhorn/orgs","repos_url":"https://api.github.com/users/schelhorn/repos","events_url":"https://api.github.com/users/schelhorn/events{/privacy}","received_events_url":"https://api.github.com/users/schelhorn/received_events","type":"User","site_admin":false},"created_at":"2015-05-12T09:40:18Z","updated_at":"2015-05-12T09:40:18Z","body":"Perhaps some clarification is in order; my reason for opening this issue was to survey pros and cons of incorporating ALT awareness into STAR. \r\n\r\nRegarding risks, reads from transcripts located at ALT contigs will confuse STAR (or, for that matter, any read mapper) and result in (unfairly) reduced mapping quality since multiple good mapping locations exist on the reference. Of course, very long read lengths may help, but waiting for them to be cost-effective for RNA-Seq probably is not the wisest course of action. In addition to the mapping quality issue, most downstream quantitation tools also punish non-unique alignments and will often not consider such alignments for estimating expression. Therefore, the full hg38 genome including ALT genomes should probably not be used with STAR at the moment, in my opinion. Of course, hg38-noalt is fine to use.\r\n\r\nRegarding opportunities, ALT contigs represent LRC/KIR/MHC loci that are highly variable across populations and of considerate interest to the immunology and immuno-oncology communities. Quantitating transcription of these entities requires aligning reads to an appropriate variation-aware reference such as hg38 in order to increase mapping rates and identify the correct haplotype. While longer read lengths may be used to rescue mapping rates by anchoring reads at invariable sequences, the identification of the haplotype that is actually expressed does not benefit significantly from longer reads if no appropriate reference sequence is available.\r\n\r\nMy point is not necessarily to push STAR development in a direction that dedicates restricted resources to support alternate reference contigs; rather I wanted to make Alex and others aware of the situation. For obvious reasons, the genomic variation community is a [little farther ahead](https://github.com/chapmanb/bcbio-nextgen/issues/817) with this that the transcriptional people since they already have an ALT-aware aligner. However, usage of alternate loci will only increase in the future once more data about pointwise and structural variation is incorporated into the reference, so the problem of alternate sequences will not go away. "}}