We have recalculated APPRIS principal isoforms for GENCODE v48 / Ensembl 114 human.

GENCODE added loss of function genes to this version and we discovered that this caused the TRIFID scores to change, affecting some of the PRINCIPAL:2 -> PRINCIPAL:5 isoforms.

Our fault, we asked for the change!

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Because of recent changes to government funding, the NIH grant that supported FlyBase has been "terminated." flybase.org

We have updated APPRIS to @gencodegenes.bsky.social v48/ @ensembl.bsky.social v114. New principal isoforms for human, mouse, rat, cow and fruit fly ( @flybase.bsky.social ).

Principal isoforms for a total of 73 human genes have been updated manually.

One example is ACOT2 where APPRIS has the correct biological isoform. The MANE Select ACOT2 isoform is almost certainly produced by an inefficient translation initiation process, would lose the mitochondrial signal sequence and will end up in the wrong compartment.
academic.oup.com/nar/article/...

Many of the novel Principal:M isoforms correspond to MANE Select transcripts because we are preferentially annotating those 1,000+ genes where MANE and APPRIS do not agree.

However, we do occasionally choose a 3rd isoform and most principal isoforms are unchanged after manual curation.

Changes to Principal:M isoforms are based on known protein structure and funcional domains, and cross-species conservation, as well as RNA-Seq and proteomics evidence.

Principal isoforms changed by manual curation are now targged as "Alternative:M".

For DCD, the Principal:2 isoform was the isoform with the intact Pfam domain. Unfortunately, the Pfam domain was based on erroneous transcript predictions in primates.

Structure and function is known for the 110 aa protein (Principal:M), while the 121 aa protein (Alternative:M) is uninteresting.

Users of APPRIS may have noticed that there is a new category of principal isoforms, Principal:M.

These principal isoforms are exclusive to the human gene set and are principal isoforms that have been manually corrected. In GENCODE v47 there were 45 genes with Principal:M isoforms.

Here is DCD:

Nice try, Luka. But even in a sham election with the real opposition candidates in jail, that is still some way short. of the 99.86% of supported ClinVar pathogenic mutations that map to APPRIS principal isoforms ...

APPRIS has updated to GENCODE v47 and mouse M36. Danio rerio has also been updated to Ensembl 113.

in this release 80.7% of human coding genes have a PRINCIPAL:1 isoform.

Also, we have begun the manual curation of principal isoforms. More soon.

@gencodegenes.bsky.social @ensembl.bsky.social

APPRIS has new annotations for GENCODE human v46 and mouse M35. The human reference set now has 16,483 genes with Principal:P1 isoforms and mouse has 18,782 genes.

Agreement with MANE Select transcripts in human (no MANE Select in mouse) has risen slightly to 17,661 genes.

appris.bioinfo.cnio.es#/

APPRIS in use ...

APPRIS has annotated principal and alternative isoforms and TRIFID functional isoform scores for Ensembl Bos taurus version e111: appris.bioinfo.cnio.es#/