# Tag Info

147

Good observation! The 3' poly(A) tail is actually a very common feature of positive-strand RNA viruses, including coronaviruses and picornaviruses. For coronaviruses in particular, we know that the poly(A) tail is required for replication, functioning in conjunction with the 3' untranslated region (UTR) as a cis-acting signal for negative strand synthesis ...

44

That is the correct sequence for 2019-nCov. Coronavirus is of course an RNA virus and in fact, to my knowledge, every RNA virus in Genbank is present as cDNA (AGCT, i.e. thydmine) and not RNA (AGCU, i.e. uracil). The reason is simple, we never sequence directly from RNA because RNA is too unstable and easily degraded by RNase. Instead the genome is reverse ...

31

This question is quite general, so I'm going to attempt to tie it back to bioinformatics. Background The tree for the current coronavirus is here, showing it is closely related to bat-coronavirus and in particular SARS. Question The bioinformatics question for the current coronavirus is why this virus appears to be able to infect humans and transmit to ...

24

The scenarios are impossible and would be laughable if they were not so serious. The evidence is in the phylogenetic trees. Its a bit like a crime scene when the forensics team investigate. We've done enough crime-scenes often going to the site, collecting the pathogen, sequencing and then analysis - (usually neglected diseases) without any associated ...

20

Some of the other answers here seem quite good; at the same time I think the core answer to the OP's question is maybe a bit hard to tease out of them, so I'd like to try to state it more plainly. It's worth noting that a truly complete answer to this question seems to be beyond current research, but any kind of "Why?" is inevitably a hard or even impossible ...

17

There area few different influenza virus database resources: The Influenza Research Database (IRD) (a.k.a FluDB - based upon URL) A NIAID Bioinformatics Resource Center or BRC which highly curates the data brought in and integrates it with numerous other relevant data types The NCBI Influenza Virus Resource A sub-project of the NCBI with data curated ...

16

Most sequencing experiments, be it Illumina-based next-generation-sequencing or Sanger sequencing uses DNA as template, not RNA. Even if this virus is RNA-based it would be reverse-transcribed prior to any sequencing experiment. Therefore the output is DNA and this is what NCBI provides here.

13

Not an expert, but some searching on eukaryotic positive-strand RNA viruses seems to show that polyadenylation is not uncommon. For example, Steil, et al., 2010.

11

UPDATE: The article has now been withdrawn with the following note: This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results. If you have any questions, please contact the corresponding author. This is very ...

10

I found a post useful for this topic. It explains the difference of coverage and depth. It also has a useful explanation on how to calculate coverage and depth. Here is a copy of what the link says just encase the post is removed: Depth of coverage How strong is a genome "covered" by sequenced fragments (short reads)? Per-base coverage is ...

9

There are several questions in your post I'll try to answer each one: Is there any way to calculate how deep the sequencing is ? See gringer's answer. TLDR: The depth of the sequencing is how many times each position has been sequenced. What should be the optimum depth to get reliable data ? The optimum depth depends on what you want to do with that ...

8

Sequencing depth is typically calculated as the number of total bases sequenced divided by the number of bases in the target genome. An Illumina sequencing run with 2x125 bp reads and 500 million read pairs sequenced would be a sequencing depth of about 40X (assuming my calculations are correct for a 3 billion base genome). The sequencing depth depends on ...

7

Normally "inserts" used in the manuscript are "indels" in protein alignments, short for insertions and deletions. What I think has happened is a group investigating indels in HIV env noticed indels in 2019-nCov. Essentially I think the correlation is spurious - but I haven't test it, but the area of research in understanding indels is certainly valid and ...

7

It seems to be explained right there in the image you posted: So, the three strains were classified based on three specific variants: Strain S, variant ORF8-L84S: a variant in the gene "ORF8" which changes the leucine (L) residue at position 84 of the gene's protein product to a serine (S). Strain G, variant S-D614G: a variant in the gene "S&...

6

Most read aligners will report unaligned reads as well, which presumably will include your viral sequences. I would ask them to formally confirm that the BAM files will contain unaligned reads before choosing that option.

6

Overview The central focus of the tree is to highlight the key biological concern of the new coronavirus, 2019-nCov. The key concern is the genetic similarities to SARS epidemic, and relates to the SARS receptor. SARS background SARS is endemic in bats (your BioRxiv tree partly shows that and this tree definitely shows it) and in the 2002 epidemic infected ...

5

R is a reference to R0, otherwise known as the basic reproductive rate, and means the number of new cases from a single patient infection. R0 has to be above 1 for a disease to persist. It is a classic equation which account for the probability of transmission against immunity. The y-axis is the number of infecteds, very poorly presented. The idea is that ...

5

There isn't a vaccine for any coronavirus, and your question is generally about targeted attentuation, which is a complex area. The basic building blocks for any vaccine development is virological understanding of the proteins involved in pathogenesis. I will focus on covid-19 as an example here. The majority of bioinformatics work is based around the ...

5

I can only speak of drug design (and even then I am terrible at turning down the jargon). In the case of drug design, this is pretty much plan C. Namely, none of compounds that entered clinical trial at the start of the year work (let's call this plan A) and none of the vaccines that are entering now clinical trial work (let's call this plan B although ...

4

This may not strike most as a bioinformatics, but getting the key clinical outcome is essential in understanding the molecular basis of pathogenicity. I think the mortality rate is over-reported. This is not to say the situation of 2019-nCov is not serious - it is very serious. The two essential factors missing in your equation for 2019-nCov are: Age. ...

4

The evolutionary related group (clade) of betacoronaviruses you have identified share an amino acid homology of 85% and include SARS. I know this from the underlying tree published on BioRxiv of a broader group of betacoronaviruses, i.e. your data is a defined subset of the betacoronaviruses which all share a unique, single common ancester. Lets call this ...

4

I don't know of any transcript-to-transcript aligners that are able to do this, but LAST can align transcript queries to protein reference sequences using a specified frameshift cost. Here's the specific documentation for that option: -F COST Align DNA queries to protein reference sequences, using the specified frameshift cost. A value of 15 ...

4

In addition to what others have suggested, I would also recommend PaVE as a resource. This is a curated database maintained by the NIAID and current holds over 300 papilloma virus genomes.

4

Since you are already using the Broad Tools sets you can use Picard FastqToSam to make the conversion As far a clipDb I am unfamiliar with that and a quick google search and look at the trimmomatic manual were unhelpful

4

If this were [cDNA], the end of the true mRNA sequence would be ...UCUUACUGUUUUUUUUUUUU, or a "poly(U)" tail. A cDNA sequence, maybe confusingly, refers to the coding strand of the cDNA (despite being called “complementary”). So while cDNA is the result of reverse transcribing RNA into DNA, by convention it has the same strandedness as the original RNA. ...

4

In summary, the authors are saying the complete opposite of "human intervention". While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding. The ...

4

My personal approach to something like this is to first try to reproduce existing work in order to learn to use relevant tools and understand the concepts involved. Then as you get more comfortable with the subject matter, you may spot an opportunity to add value. If you'd like to get started with the phylogenomics side of things, you can use this public ...

3

If you are interested in a particular viral sequence, it seems wasteful to request bams that are aligned to the human genome, but you could request bams aligned to the human genome with unaligned reads retained. As an alternative, you can generate unaligned bams, where all of the same reads are present that would be present in a fastq but in a bam format. ...

3

It's not common to sequence directly from RNA because most sequencing platforms don't have that as an option. Nanopore sequencers do allow this, but I'm not aware yet of any 2019-nCov preprints involving nanopore RNA sequencing. I expect that will change in the next month or so. Commercial kits exist; there are no insurmountable technical issues with it. ...

3

R, the reproductive number, relates to the average number of (new) people that will get sick (infected) per person that is already sick. For instance, if $R=2$ and you start with a single infected person, then the next generation will be 2 people, those 2 people will make 4 people sick, those 4 people will make 8 people sick, and so on. Is R a fixed ...

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