tag:blogger.com,1999:blog-37148773.post1020391543189451801..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: How many protein-coding genes in the human genome?Larry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger16125tag:blogger.com,1999:blog-37148773.post-69644777779018262442018-08-15T03:48:13.450-04:002018-08-15T03:48:13.450-04:00A new paper that suggests the number of coding gen...A new paper that suggests the number of coding genes may be less than 20000.<br /><br />https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky587/5047265<br /><br />CNhttps://www.blogger.com/profile/16662377337824094350noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-62279667272120079322018-07-18T20:24:23.875-04:002018-07-18T20:24:23.875-04:00Presumably whether a sequence is classified as cod...Presumably whether a sequence is classified as coding or non-coding is going to affect 1. its probably of being sequenced as part of a diagnostic test and 2. the type of analyses any mutations within the sequence will be subjected to in looking for causal genotype-phenotype relationships. So has there been enough diagnostic whole genome sequencing done that one can estimate what fraction of disease causing mutations are identified by whole genome sequencing that would have been missed by whole exome sequencing? Along the same lines are there estimates of what fraction of mutations initially identified as variants of unknown significance are ultimately classified as benign?<br /><br />Anonymoushttps://www.blogger.com/profile/02484186057476833733noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-30544580773273564802018-07-18T17:53:24.305-04:002018-07-18T17:53:24.305-04:00Mutations that are medically relevant can occur in...Mutations that are medically relevant can occur in protein-coding genes, noncoding genes, other functional elements in the genome, and in junk DNA. We need to have an accurate picture of everything in the genome in order to interpret genetic variants that have phenotypic effects. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-33523709017061183102018-07-18T17:15:59.336-04:002018-07-18T17:15:59.336-04:00In my experience, I find that dealing with too muc...In my experience, I find that dealing with too much rubbish (alternative transcripts, wrong protein-coding genes, bunch of non-coding genes, so many chip-seq peaks, etc, etc) makes you waste a lot of time and makes difficult to identify relevant signals. <br /><br />For example, when studying germline variants the ones of highest interest are usually the ones with highest impact on protein-coding. Well, these variants happen much more frequently in alternative transcripts that are very unreliable (and they happen because those transcripts are not under negative selection); investigating them is a waste of time (in my opinion).Federico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-91168921602787251862018-07-18T17:05:41.796-04:002018-07-18T17:05:41.796-04:00How long is a piece of string?
Both are importan...How long is a piece of string? <br /><br />Both are important, but require different strategies. The paper concentrated on coding genes that may not code for proteins. At the same time GENCODE manual annotators have added 137 new coding genes just in the last year, https://www.biorxiv.org/content/biorxiv/early/2018/07/02/360602.full.pdf).<br /><br />However, I do think that at this moment there are many more misclassified coding genes in the human genome than there are missing coding genes. Michael Tresshttps://www.blogger.com/profile/10775168466643478973noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-34093916943282311952018-07-18T13:46:38.865-04:002018-07-18T13:46:38.865-04:00"The set of human coding genes needs to be as..."The set of human coding genes needs to be as complete as possible for biomedical experiments, but inevitably some genes will be misannotated as coding."<br /><br />Presumably some genes will also be misannotated as non-coding. So I guess the question is which type of error would be considered more serious for medical experiments?Anonymoushttps://www.blogger.com/profile/02484186057476833733noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-91038355017578650542018-07-18T04:23:33.922-04:002018-07-18T04:23:33.922-04:00Cell biology by the numbers:
http://book.bionumber...Cell biology by the numbers:<br />http://book.bionumbers.org<br />Federico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-1440853207810809762018-07-18T03:54:51.384-04:002018-07-18T03:54:51.384-04:00How many proteins in the human proteome?<a href="http://sandwalk.blogspot.com/2016/12/how-many-proteins-in-human-proteome.html" rel="nofollow">How many proteins in the human proteome? </a>Corneelhttps://www.blogger.com/profile/02884855837357720225noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-46207188083520936092018-07-16T23:38:11.954-04:002018-07-16T23:38:11.954-04:00Professor Moran
How many different types of prote...Professor Moran<br /><br />How many different types of proteins have a human been adult?<br />20,000 ? and how many other molecules?<br />Thanks<br />Sorry by my english im from spainPalermo Rhttps://www.blogger.com/profile/10441950854597711723noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-6971202151876273882018-07-16T16:33:29.853-04:002018-07-16T16:33:29.853-04:00Thank-you for pointing out the typo. I fixed it. Thank-you for pointing out the typo. I fixed it. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-18245675139795445992018-07-16T13:46:48.256-04:002018-07-16T13:46:48.256-04:00Professor Moran
How many different types of prote...Professor Moran<br /><br />How many different types of proteins have a human been adult?<br />20,000 ? and how many other molecules?<br />Thanks<br />Sorry by my english im from spainPalermo Rhttps://www.blogger.com/profile/10441950854597711723noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-85919731449280086142018-07-16T07:56:11.236-04:002018-07-16T07:56:11.236-04:00I should also probably point out that the work tha...I should also probably point out that the work that we had to do to clean up UniProt was not because it had more errors, but because UniProt is a protein-centric database, while GENCODE and RefSeq are genome coordinate-based. There wasn't always a 1-to-1 equivalence between Uniprot protein entries and RefSeq/GEMCODE gene entries and this often had to be fixed manually. Thanks again.Michael Tresshttps://www.blogger.com/profile/10775168466643478973noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-12601055570393933062018-07-16T06:18:07.485-04:002018-07-16T06:18:07.485-04:00Thanks for discussing our paper, Larry, it's a...Thanks for discussing our paper, Larry, it's a fair summary of it!<br />The only bit which isn't right is "Evidence of positive selection was assayed by looking at variants (alleles) in 2504 human genomes. The questionable protein-coding genes had many more variants than real genes, suggesting that they are not under strong positive selection. “ We looked for evidence of negative selection (=purifying selection), not positive selection. When you don't see evidence for negative selection there may be three causes: a) lack of power ; b) positive selection; c) neutral evolution. In our case we could discard lack of power because many genes were tested altogether. We cannot entirely rule out positive selection, but is very unlikely that positive selection is acting on so many strange genes. The most parsimonious interpretation is that most of those genes are evolving neutrally in the human population (at least neutrally with respect to the mode of evolution of protein-coding genes; they may be noncoding genes evolving under purifying selection, we cannot say anything about that)<br />Federico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-34528696442669290252018-07-14T14:26:18.597-04:002018-07-14T14:26:18.597-04:00I edited the phrase "under negative selection...I edited the phrase "under negative selection with potential homologues" to "under negative selection with respect to potential homologues."Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-76418866820749263952018-07-14T14:23:10.781-04:002018-07-14T14:23:10.781-04:00If it's a real gene there will be less variati...If it's a real gene there will be less variation than if the sequence is junk and evolving neutrally. In other words, the real gene will be "conserved" because it's under negative selection. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-75890856546898355362018-07-14T13:51:50.230-04:002018-07-14T13:51:50.230-04:00"The next best evidence is that the putative ...<i>"The next best evidence is that the putative gene is under negative selection with potential homologues in other species."</i><br /><br />Don't you mean purifying selection? I take negative selection to mean it is selected against. Mikkel Rumraket Rasmussenhttps://www.blogger.com/profile/07670550711237457368noreply@blogger.com