Hello everybody and welcome to today's webinar.
Today we are talking about gene and protein, chemical names and aliases, synonyms and other
confusing terms.
Rana Morris is going to be giving the webinar.
This is Peter Cooper.
The directory for the slides and Q&A document will be on the FTP site.
That go.usa compressed URL will take you there.
I'm going to turn this over to Rana now and she will talk about chemical and protein and
gene names and aliases.
Hello and welcome.
This NCBI Minute is based on two Insights blog posts on topics that many users have
asked us about previously.
I will show you how to find those at the end of the presentation.
As science progresses what we call things can change over time.
Gene symbols, protein names, what we call chemical compounds.
This can be confusing not just when conversing about scientific research but particularly
when looking for and at articles that have been published over time.
In this NCBI Minute I'll give a couple quick examples about how the use of names and terms
can be confusing.
I will show you how we deal with that issue in house, where we put the information on
our webpage so that others can benefit from our work, and show you some of the FTP files
that you can download if you want to get this information in bulk.
Two of the main groups that handle this nomenclature issue here at NCBI deal with assigning terms
for genes and proteins and chemical compounds.
A classic example of a problem with gene symbols is shown here.
I found a paper published in 1999 describing the effect of a gene product called p21sdl1
in four different cancer cell lines.
In 2010 another paper describes the gene p21Cip1 in a CML cancer study.
Two years later, p21Waf1 was examined for it’s effect with Estrogen Receptor α in
6 breast cancer cell lines.
These genes are actually all the same.
There are many papers that have actually concatenated these terms in various combinations: Cip1/Waf1,
Waf1/Sdl1, p21/Cip1.
It’s not even really just use based on an evolution of the term through time, since
there was a publication back in 1994 which concatenated all of the various possibilities
together in one swell foop.
Last year a publication came out describing the effect of CDKN1A in thyroid cancer.
Guess what?
It’s also the same gene.
In fact, the Official Gene Symbol as designated by the Human Gene Nomenclature Committee is
actually CDKN1A – which is the symbol for the cyclin-dependent kinase inhibitor 1A.
All the other terms that have been used are now known as aliases or synonyms or also
known as terms for the same gene and gene-product, which in this case is a protein.
A similar and, perhaps, more long-running problem has occurred in the world of chemicals.
Here’s the most accurate “name” for a chemical – actually it is the 2D view
of the atomic structure.
But early in it’s research life it was designated with various code-terms.
When the structure is known, it can have an official nomenclature-designated (IUPAC) name
and there is often a registry identifier designated for it (like CAS).
Over time, this was identified as an important compound and given a more easily pronounceable
and marketable name, Tamoxifen.
Although various companies decided to sell forms of it under other names.
What do you do with all of this?
How do you look it things up in a literature search?
What do you search with if you want to find something to buy?
So how does NCBI deal with this situation?
We’ll start with terms for Genes & Proteins.
We have a curation group at NCBI called RefSeq – the Reference Sequence project.
This is a group of curators who examine the literature and work with collaborators in
the community along with automated data-gathering processes to compile a list of terms that
have been used for a particular gene or protein.
This includes an officially designated Gene Symbol and protein name – when one exists,
along with all of the other terms that have been used for it in the literature,
in reputable databases such as UniProt, PDB and SwissProt, and from submissions from Experts
in the field.
We display compiled lists of all of these on records in the Gene database.
Gene Symbols are shown in the Summary section at the top of the page, with the Official
Gene Symbols designated and others that have been used listed in the Also known as section.
Protein names are listed in the General Protein Information, Names section,
with an Official name designated along with others shown below.
Here’s an example for the CDKN1A gene.
Here’s the Gene page for CDKN1A (cyclin-dependent kinase inhibitor 1A) - the human one.
Just to remind you, there is a Table of Contents on the right that lists all of the sections
of this record.
In the top section is the Summary, which lists the Official Gene Symbol and Protein
name.
The organization that made the decision is listed right here.
In this case, this was decided by the Human Gene Nomenclature Committee – the HGNC.
Other alias Gene Symbols that have been used in history are listed in the Also Known As
section.
Further down the page, you’ll find Protein Names listed in the General Protein Information
section, under Names and Preferred Names.
While the RefSeq Group deals with Genes & Proteins, we have another group that deals with Chemicals.
The PubChem Group has automated processes that aggregate all of those terms that have
been used for Chemical Compounds.
Aliases or Synonyms for chemicals are compiled from MeSH Indexing curators at NLM and from
submitters of chemical data to PubChem.
In addition, you may remember from your old organic chemistry class, that there are several
different nomenclatures used for chemicals based on their atomic structure.
We have a software program that will actually compute these terms based on the chemical
structure and these are called, Descriptors.
These include our old friend (or nemesis), IUPAC, as well as several others such as InChI,
InChI Key, SMILES and SMARTs.
Finally, we aggregate Identifiers that are used by various organizations such as FDA’s
UNII term, the EU’s European Chemical Agency’s Number, and others.
These are placed on PubChem Compound record pages in a Names & Identifiers section.
Here’s an example for Tamoxifen.
Here’s the PubChem Compound page for Tamoxifen.
The record has a top Summary section, which is pretty helpful.
PubChem puts it’s Table of Contents on the left - listing all of its sections
(and they are expandable for a multi-level outline view).
It’s the 3rd section that lists those Names & Identifiers that have been aggregated and
calculated.
First come the Computed Descriptors, which are generated from the chemical structure
– IUPAC, InChI, InChI Key and so on….
Then below that is the Other Identifiers list including a CAS Registry number (when we have
it), an EC Number and the FDA’s UNII, for example.
Then, the Synonyms section includes those compiled by MeSH Curators at the NLM
and a list collected from all of the submitter's of information to PubChem.
Note that you can DOWNLOAD the information in this record at the top of the page.
You can also do this back on the GENE record page.
But what about if you want to download, not just one Gene or Chemical’s information,
but a whole bunch of it all at once?
Back to Genes & Proteins.
In addition to displaying those also known as and names directly on the Gene record pages,
the RefSeq Group also produces several files that they regularly update on the NCBI FTP
site.
These are tab-separated text files containing lots and lots of information.
These include Gene Symbols and Protein Names among a lot of other cool stuff.
These are called GENE_INFO files.
Here’s the full path to find the Gene_Info files on our FTP site.
To help visualize this, they are located in the Gene database folder, in the DATA folder,
in a GENE_INFO subfolder.
You can get the ALL_Data.gene_info.gz file which provides lots of information for ALL
the organisms listed in the Gene database.
Alternatively, you can get an organism-specific file, which is much smaller and is, frankly,
what most people want.
For example, you can go into the Mammalia subfolder and then select the Homo_sapiens.gene_info.gz
file to get only the information about Human genes.
Note that we also have files specifically for Mouse, Rat, Dog, etc.
Also, please note that these are pretty large G-Zipped (compressed) files.
What do these files look like?
Well they are made up of 15 tab-separated columns with lots of information.
I’ve turned the table over 90-degrees and have shown only a few columns here, because
I think it make it easier for you to see what we have.
Here’s an example of the data pertaining to
the CDKN1A gene or cyclin-dependent kinase inhibitor 1A that I showed you earlier, showing:
the Gene database identifier (GeneID), correlated Gene Symbols and then the names designated
for that particular gene product.
Please note that the organism-specific ones are easily importable into Excel or parseable
with even much more helpful data about the genes I'm not showing here.
And you can keep, discard or reorganize the columns however you want.
While gene and protein information is the charge of the RefSeq Group, remember that
chemical information is gathered by the PubChem Group and displayed on PubChem Compound records.
The PubChem Group also produces helpful FTP files which are, perhaps, even easier to use
to correlate Synonyms for a Chemical Compound.
There is a single file on the NCBI FTP site which has only 2 tab-separated columns –
with the PubChem Compound Identifier (or CID) in the first column and then a corresponding
Synonym in the second.
However, if you are interested in those other terms used for chemicals – Computed Descriptors
and Identifiers – you’ll need to download the full PubChem
Compound database record file to get all of those.
So where are they?
Here’s the full path to find the PubChem files on our FTP site.
To help visualize this, they are located in the PubChem database folder, in the Compound
folder, and then the Extras subfolder – there are a lot of really nice and helpful
files.
You can access the CID-Synonym-filtered.gz file, down here at the bottom, to get a cleaned
list of all of the Synonyms provided to PubChem for chemical compounds.
The G-Zipped (compressed) file is pretty big (almost a Gigabyte), but it is a simple file
containing only 2 columns: the CID & the Synonym.
There are other files in this Extras folder that may be of interest, such as the CID-MeSH
file which shows only the single MeSH-preferred term for the chemical
(which we use for the name at the very top of PubChem Compound records).
For all of those other Computed Descriptors and Identifiers, you’ll need to go to the
Compound CURRENT-Full record files.
They are produced in several formats, so you can get whichever one is best for you: ASN.1,
XML or SDF.
Here’s an example of a portion of the Tamoxifen data in the SDF-formatted file.
Embedded in the data are IUPAC Names, INCHI & INCHI KEY terms, SMILES terms and lots of
other data.
Now, you don’t have to remember all of this or have to watch this video again.
ALL of this information has already been written up with descriptions and links in two NCBI
Insights Blog posts.
The NCBI Insights Blog provides information about NCBI resources with tips & tricks to
help you use our site and make cool discoveries.
One NCBI Insights Blog post fully explains how to get the Also known As terms for Genes
& Proteins.
Another talks about how to get Chemical Synonyms (and even mentions simple APIs that you can
use, if you prefer those to downloading large files).
I’ve included bit.ly links here to make them easy to find.
But you can always check in on or search the NCBI Insights Blog site for
more cool tips & tricks.
Many helpful How to videos are - and this one soon will be –
available on our YouTube channel.
And, as always, if you have any questions about or need help with our resources –
send an Email to our HelpDesk at info@ncbi.nlm.nih.gov .
Thanks for your attention.
[Peter Cooper] Thanks Rana.
We have time for a few questions.
I see -- I answered one in the question pod that I think everybody has seen.
The other one was about where you can get a copy of the slide deck.
Well, that [sic] bit.ly (go.usa.gov) link on the cover slide has that and I will put
that in the question pod in a minute.
Okay, we have one more question in the question pod.
How often do the gene and protein databases update the synonyms and identifiers?
[Rana Morris] I'm not sure about the gene, I'll have to get back to you on that.
PubChem updates those files every day.
When new information comes in it takes a couple days to process and then that file is updated,
I think, at 7 PM every night.
That is constantly updated.
I believe the gene record is updated a little less frequently but still pretty well and
we can find that information out.
Send an email to info@ncbi.nlm.nih.gov and we will get that information to you.
[Peter Cooper] I sent out the compressed URL to that FTP site that has the slide deck,
to everyone.
Another listener, from NCBI, has chimed in.
The GENE_INFO file on the FTP site seems to be updated daily as well.
I don't see any other questions and we are out of time so I'm going to wrap up the webinar.
Thank you for attending and Rana, thank you for providing this webinar, and we will see
you next time.