User talk:Slashme

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There is currently a discussion at Wikipedia:Administrators' noticeboard/Incidents regarding an issue with which you may have been involved. Thank you.

Dear Slashme,

Thanks for your review in the page valuation (auditing), however, i would like to request for some clarification in this topic.

Valuation (finance): is the process of determining value of assets and liability by the management appearing the balance sheet of the company whereas valuation (auditing): is the review process of value determined by the management of the assets and liability appearing in the balance sheet.

They are distinct concept and related with independent field of study. Need your coordination and consideration

Thanks in advance Nirjal Shrestha

Hi Slashme

I wrote the original section called gene of uncertain significance that has been rolled into variant of uncertain significance. I assume I can go ahead and modify the variant of uncertain significance section?

The key points I tried to connect together when I wrote the section were:

1. lots of people are being sequenced and we are finding a lot of sequence differences among people
2. geneticists don't like to call a difference from the normal sequence 'mutation'
3. we prefer the word variant because a difference that causes disease is pathogenic while one that does not hurt you is benign - hence benign variant and pathogenic variant
4. getting all labs to agree on what scientific evidence is needed to call something a pathogenic variant is critical
5. there is a huge effort to establish these guidelines by labs around the world and several committees have published on this - example^[1]
6. A 5 tier classification system was developed that classified a variant for a gene that is a well known to cause disease (example: CFTR causes cystic fibrosis)
7. All of the above is the history leading up to the invention of the term GUS by the working group^[1]
8. Application:

We known where in the body every gene in humans is expressed so we know a something about the function of every gene in humans. But only 5000 of the 20,000 genes in humans have been connected to a disease. To put it another way, there are 2 types of gene. Genes that have been connected to a disease such as CFTR which causes cystic fibrosis and genes that have not been connected to a disease such as RNF4. We don't know of a human (yet) who has a disease caused by mistakes (pathogenic variants) in RNF4.

If you have a gene that has been connected to a disease such as CFTR and cystic fibrosis when you find a change in the CFTR gene you need to figure out if the change causes that copy of the gene to malfunction. If it is a change that cause that copy of the gene to be 'broken' such as a premature stop or a frameshift then it is a pathogenic variant. But sometimes we find a change and we don't know if it inactivates the copy of the gene that it is in or not. When we don't know what the change will do that is a variant of uncertain significance (VUS). We only apply VUS and the other 4 categories when we KNOW what disease is caused by mistakes in the gene.

The committee had to invent a term (GUS - gene of uncertain significance) for situations where the gene has NEVER been connected to a human disease such as RNF4. All we know about RNF4 is that a mouse with mistakes in the gene has heart defects and dies in utero.^[2] So let's say a lab did whole genome sequencing on a human fetus that had died in utero and at autopsy they found heart defects. And let's further suppose that the lab found a frameshift variant in both copies of the RNF4. Well, we know that both copies of the RNF4 gene do not work because frameshift variants kill the gene's function. But we STILL don't know that we have the answer because no one has ever connected RNF4 to a HUMAN disease! The lab would report this as a GUS because it thinks it has the answer but can't prove it. Labs do NOT try to use the 5 tier classification if the gene is a GUS because it is misleading to designate something a pathogenic GUS or a VUS GUS in a lab report.

The importance of the Wiki entry lies in the fact that thousands of people are having their genome sequenced now and there is a growing group of individuals who want to analyze their own genome. They will turn to Wiki to understand some of basic concepts needed to understand the medical literature concerning how labs classify variants.

DavidDpaulbick (talk) 02:00, 22 January 2017 (UTC)[reply]

Hi David,

I did some formatting of your comment above; I hope you don't mind!!

Anyway, you have absolutely as much right as anyone to edit the VUS article. I think the points that you make are quite valid, and we should find a way to communicate them. Exactly how we word things, and how much weight we give to what, will be thrashed out over time and develop out of consensus. Nothing needs to be perfect from the start on Wikipedia. The only time that you shouldn't be editing any particular article on Wikipedia is if you have a conflict of interest, or if the community has told you that you're being disruptive, and should step back. Even then, if you think that the community is wrong, there are plenty of ways to ask for more input or to appeal against what has been said before.

Have fun, and thank you for your contributions! I think it's best to keep the discussion of this topic at Talk:Variant of uncertain significance, so that everyone editing the article can join in the discussion. --Slashme (talk) 13:13, 22 January 2017 (UTC)[reply]

@Dpaulbick:Yes, I agree with slashme. Have fun editing VUS! DennisPietras (talk) 17:02, 31 January 2017 (UTC)[reply]

The feedback request service is asking for participation in this request for comment on Talk:Earthquake prediction. Legobot (talk) 04:28, 27 January 2017 (UTC)[reply]

Skipping: this discussion is by now well covered by people who know much more about the topic than I do. --Slashme (talk) 08:03, 27 January 2017 (UTC)[reply]

Hi "pal". Well, it's been a week, and judging from the lack of replies at VUS, I'd be willing to bet that jytdog is one of the few people who care a lot about primary sources! (S)he and I have apparently agreed to disagree while staying on our own sides of the line in the sand, which should promote prolonged peaceful coexistance. I added a supplementary viewing section to VUS, in case you aren't folllowing it. DennisPietras (talk) 16:59, 31 January 2017 (UTC)[reply]

@DennisPietras: Thanks for this! I've responded at the talk page; let's see how this pans out. As you know, I'm all for peace :-]. --Slashme (talk) 19:27, 31 January 2017 (UTC)[reply]

@DennisPietras: I see WhatAmIDoing has weighed in on the sources, so that's good for discussion. (S)he's making the important distinction between sources supporting medical facts and sources supporting general facts. --Slashme (talk) 19:31, 31 January 2017 (UTC)[reply]

Hi, I'm Iazyges. I wanted to let you know that I saw the page you reviewed, Alessandro Velotto, and have un-reviewed it again. If you have any questions, please ask them on my talk page. Thank you.

Iazyges Consermonor Opus meum 12:57, 3 February 2017 (UTC)[reply]

Hi Iazyges, can you give more detail about why you unreviewed that article? It seems to pass WP:NSPORT, it's not a completely unsourced BLP, and it's tagged as only having one source. Why should it still be in the new pages feed? --Slashme (talk) 14:31, 3 February 2017 (UTC)[reply]

As you can tell from the article's revision history, I created it as a redirect to the list of Pokemon 7 years ago and have not touched it since. An IP editor has since been trying to make it an article about some actor. If the article about said actor is unfit for Wikipedia, the correct course of action would be to simple revert it back to a redirect, proposing it as deletion I feel is overkill, and sending the article creator, me, a notification about it when it has really nothing to do with me is annoying. Please refrain from doing this, thanks _Blake ^{(Talk·Edits)} 18:17, 3 February 2017 (UTC)[reply]