a***s
发帖数: 1084 | 1 据说提高了亲水性，获得被当作艾滋病毒的缺点。
这亲水性的提高显然增强了传播能力啊。 | H********g
发帖数: 43926 | 2 三哥论文链接有吗
【在 a***s 的大作中提到】
: 据说提高了亲水性，获得被当作艾滋病毒的缺点。
: 这亲水性的提高显然增强了传播能力啊。
| H********g
发帖数: 43926 | 3 发信人: qiing (契旲), 信区: Military
标 题: 阿三大嘴PPT，你们也信？
发信站: BBS 未名空间站 (Sat Feb 1 12:24:32 2020, 美东)
http://theprepared.com/blog/no-the-2019-ncov-genome-doesnt-actually-seem-engineered-from-hiv/
2019-nCoV genome doesn’t really seem engineered from HIV
A group of bioinformaticians at two prestigious universities in Delhi, India
, published a preprint scientific manuscript on the bioRxiv preprint server
Friday has led many to speculate wildly that 2019-nCoV may have been
deliberately engineered using HIV protein sequences.
The paper, entitled “Uncanny similarity of unique inserts in the 2019-nCoV
spike protein to HIV-1 gp120 and Gag,” presented a sequence alignment
analysis of the unique elements of the 2019-nCoV genome which noted some
similarities to elements of the HIV genome. The authors seemed to suggest
that these similarities couldn’t have arisen randomly, so people can be
forgiven for jumping straight to “it’s a bioweapon” after reading it.
But having read the paper, I still don’t find this bioweapon argument
convincing, and despite this new paper’s language, a random sequence
overlap is still the leading explanation for sequence alignment it
identifies with HIV.
Take this to the bank: 2019-nCoV continues to give every appearance of being
a wild coronavirus that jumped from bats to humans by way of an animal
intermediary in the Huanan seafood market in Wuhan in late 2019. It is not
an escaped bioweapon.
Author’s note: I have a Ph.D. in bioinformatics, and am a principal data
scientist at a major pharmaceutical company. This paper isn’t directly in
my wheelhouse, but it’s pretty close.
What the Indian group did
The new paper’s authors took 28 sequences of the 2019-nCoV genome isolated
from 28 different patient samples, and aligned them with the bat coronavirus
genome which is 2019-nCoV’s closest known relative. Although the two viral
genomes are 96% identical, this leaves about 1200 DNA bases, and a smaller
number of protein residues, where they differ.
Among the differences, the Indian team identifies four insertions, where the
2019-nCoV genome contains a small extra sequence corresponding to a few
additional amino acids in an otherwise similar protein. These insertions are
as short as 6 residues.
All four insertions were located in the “spike protein” of 2019-nCoV, the
projecting protein on the virus’s round envelope which recognizes the ACE2
receptor and enables the virus to penetrate mucous membrane cells, and also
gives the coronavirus its name. The variable sequences of these recognition
regions enable viruses to penetrate different types of cells in the human
body.
The authors took the 2019-nCoV version of the spike protein sequence, and
performed homology modeling to generate a likely 3D structure of the spike
protein, using known 3D structure of the spike protein from the SARS virus
as a starting point. They found that although the four sequences are distant
in the 1D chain of the protein, the folding of the spike protein brings
three of them together in 3D space, and that they are on the “tip” of the
spike, at the ACE2 recognition site.
The authors then use the pBLAST sequence alignment tool to identify any
sequences from any known viral genome that look similar to the short
sequences identified from 2019-nCoV. They searched the National Center for
Biotechnology Information’s viral genome database, which contains over
three million viral genome sequences.
They found that all four of these spike protein inserts appear as matches to
at least one sequence in at least one variant of the HIV virus. The
sequences come from the gp120 and Gag proteins in HIV, the former of which
is also a viral envelope recognition protein. This has led many to
credulously assume that this is evidence, or even a strong indication, that
2019-nCoV was engineered from its bat ancestor by humans inserting HIV
sequences.
No, 2019-nCoV is still not an escaped bioweapon
But they’re wrong; it’s still not engineered. An analysis of the paper
clearly reveals that:
There is nothing remarkable about the fact that 2019-nCoV’s sequence
diverges from its nearest known relative, or that its unique sequences are
conserved among cases of 2019-nCoV.
The sequence matches with HIV are very short and appear in hypervariable
regions of both virus, and similar overlaps are seen between 2019-nCoV
sequences and many other organisms.
The unique biological properties that HIV sequences could theoretically
impart to another virus are completely missing from 2019-nCoV, and 2019-nCoV
has no unique clinical properties that are outside what is known to be
possible for a coronavirus.
In other words, the sequence overlap is not actually uncanny, and there is
no big scoop here. The group in India fell prey to some of the pitfalls of
bioinformatics research.
There’s no genomic or clinical anomaly that needs explaining
The 2019-nCoV genome does not contain remarkable genomic properties which
need explaining, and for which we’d look to some kind of bioengineering as
a cause.
The virus has a close 96% sequence overlap to a naturally occurring bat
coronavirus, and coronaviruses have been known to jump from bats to humans
by way of intermediates before, like the SARS coronavirus. The differences
between the genome sequences, including the ones identified by the Indian
study, are in variable regions of the genome that we’d expect to differ,
and the 4% difference in the genomes is hard to call as “high” or “low,”
given that we don’t know exactly which bats the 2019-nCoV strain came from
or when it diverged from its closest known ancestor.
Nor is it surprising that the known 2019-nCoV sequences all contain the same
genomic changes relative to a known relative. They all came from the same
outbreak from the same animal reservoir, i.e. they only diverged from each
other a few months ago at most. It’s not surprising that they haven’t
evolved very much away from each other.
Nor does the clinical presentation of 2019-nCoV have novel features which
need explaining. Its symptom profile, degree of transmissibility, severity,
mortality rate, duration, incubation and latent period, ability to jump from
animals to humans, and ability to transmit asymptomatically and by skin
contact are all within the precedents established by other human
coronaviruses.
That is, the 2019-nCoV genome and the way it affects humans have, by
themselves, no special anomaly which needs explaining.
The sequence overlap is not remarkable and is probably random
Worse, though, the HIV sequence overlap is not particularly remarkable.
The insertions are as short as 6 peptide residues long, and the two which
are longer are not identical matches.
Very short sequences are not really what pBLAST was designed for, especially
not when searching huge databases. Looking through three million viral
genomes for a sequence that short means you’re bound to find something, and
other scientists have pointed out in the hours since the Indian paper was
posted that similar overlaps, just as strong, may be found in a wide variety
of viruses, and also bacteria, protists, fungi, fruit flies, and plants.
The overlap to HIV is not to a “characteristic” HIV region that is
conserved among HIV, but to particular samples (in fact, three different
ones from three different countries). They’re just the flotsam and jetsam
of variable regions generating a lot of different sequences which get picked
up in mass sequencing efforts, not a smoking gun.
In particular, the sequences identified both come from short alpha helical
regions on the surface of an envelope/membrane protein, and both feature a
lot of positively charged polar residues. These kinds of similar residues
have a tendency to appear together on sequences of this type, increasing the
chance that unrelated sequences may share short overlaps if they both come
from this type of protein domain.
The sequence alignment charts of these variable regions of the spike
proteins of known coronaviruses from the Indian paper is a good example of
this, as the “alignment” is an alphabet soup of wildly variable sequences
from different coronaviruses, with no real consistency. The genome database
for all organisms is an ocean of this kind of alphabet soup, and the kind of
overlap we’re talking about isn’t Hamlet, or even full sentences, but
just a few words.
There’s no special effect for this overlap to achieved
On a clinical level, too, there’s no link between these two things. The
coronavirus spike protein and the HIV gp120 protein are both recognition
proteins on the envelope surface, but they’re very different. The spike
protein allows the coronavirus to recognize the ACE2 receptor and invade
mucous membrane epithelium, while the gp120 protein allows the HIV virus to
recognize the CD4 receptor and invade CD4+ T-cells. The Gag protein on HIV,
host of the fourth matching sequence recognized by the Indian team, is in
the interior of the virus.
So, if the hypothesis were true, you might expect the 2019-nCoV strain to be
able to infect T-cells or recognize the CD4 receptor. But there is no
evidence so far that 2019-nCoV can infect T-cells, or that it can infect any
cells expressing CD4, or that it can infect any cells which don’t express
ACE2 or can’t be infected by other known coronaviruses.
The epidemiology still suggests animal (zoonotic) origin, not an escaped
weapon
Human nature, crowd psychology, the availability heuristic of this storyline
from fiction, and a bunch of other factors have made the “escaped
bioweapon” storyline appear over and over, and spread like wildfire when it
does. But there’s no evidence it’s true.
2019-nCoV continues to give every appearance of being a wild coronavirus
that jumped from bats to humans by way of an animal intermediary in the
Huanan seafood market in Wuhan in late 2019. | a***s
发帖数: 1084 | 4 蝗虫有结论吗？这是不是亲水性提高了？
[在 Huangchong (净坛使者) 的大作中提到：]
:http://theprepared.com/blog/no-the-2019-ncov-genome-doesnt-actually-seem-engineered-from-hiv/
:A group of bioinformaticians at two prestigious universities in Delhi,
India, published a preprint scientific manuscript on the bioRxiv preprint
server
:Friday has led many to speculate wildly that 2019-nCoV may have been
:deliberately engineered using HIV protein sequences.
:The paper, entitled “Uncanny similarity of unique inserts in the 2019-nCoV
:spike protein to HIV-1 gp120 and Gag,” presented a sequence alignment
:analysis of the unique elements of the 2019-nCoV genome which noted some
:similarities to elements of the HIV genome. The authors seemed to suggest
:that these similarities couldn’t have arisen randomly, so people can be
:forgiven for jumping straight to “it’s a bioweapon” after reading it.
:.......... | H********g
发帖数: 43926 | 5 还没仔细看
另外 亲水疏水 这种概念 跟病毒的特性 没有关系
nCoV
【在 a***s 的大作中提到】
: 蝗虫有结论吗？这是不是亲水性提高了？
: [在 Huangchong (净坛使者) 的大作中提到：]
: :http://theprepared.com/blog/no-the-2019-ncov-genome-doesnt-actually-seem-engineered-from-hiv/
: :A group of bioinformaticians at two prestigious universities in Delhi,
: India, published a preprint scientific manuscript on the bioRxiv preprint
: server
: :Friday has led many to speculate wildly that 2019-nCoV may have been
: :deliberately engineered using HIV protein sequences.
: :The paper, entitled “Uncanny similarity of unique inserts in the 2019-nCoV
: :spike protein to HIV-1 gp120 and Gag,” presented a sequence alignment
| t******g
发帖数: 10390 | 6 这个hiv类似性不是已经在biorxiv的comments里给批判了吗?
很短的4个片段,平均7,8个氨基酸的样子,单个片段去基因库里blast能找出一堆一堆的,
他们只限定在特定的病毒库里,就算是病毒库,不光hiv有,也很多不相干的病毒有,比如
一些植物病毒,他们的那个uncanny similarity完全是主观判断.或者说是方法上有缺陷.
其中3个片段在结构上靠近,这个也是常见的,高可变区,这里变化不影响病毒传代.
另外,有人也说了,hiv里面他们找到的相同片段,在hiv的结构里完全不在一起.
这个biorxiv上有多少是投了以后才贴上去的,冷泉港搞这个不觉得会制造这种假新闻吗
?【 在 alias (贾人贾义) 的大作中提到: 】 | H********g
发帖数: 43926 | 7 biorxiv本身是好的 民科自己瞎搞不能赖冷港
而且biorxiv可以评论 光这就比期刊好不知到哪里去了
的,
陷.
【在 t******g 的大作中提到】
: 这个hiv类似性不是已经在biorxiv的comments里给批判了吗?
: 很短的4个片段,平均7,8个氨基酸的样子,单个片段去基因库里blast能找出一堆一堆的,
: 他们只限定在特定的病毒库里,就算是病毒库,不光hiv有,也很多不相干的病毒有,比如
: 一些植物病毒,他们的那个uncanny similarity完全是主观判断.或者说是方法上有缺陷.
: 其中3个片段在结构上靠近,这个也是常见的,高可变区,这里变化不影响病毒传代.
: 另外,有人也说了,hiv里面他们找到的相同片段,在hiv的结构里完全不在一起.
: 这个biorxiv上有多少是投了以后才贴上去的,冷泉港搞这个不觉得会制造这种假新闻吗
: ?【 在 alias (贾人贾义) 的大作中提到: 】
| t******g
发帖数: 10390 | 8 显然很多不懂行的人把这个老印的文章当正式发表的科学论文了啊.
【在 H********g 的大作中提到】
: biorxiv本身是好的 民科自己瞎搞不能赖冷港
: 而且biorxiv可以评论 光这就比期刊好不知到哪里去了
:
: 的,
: 陷.
| H********g
发帖数: 43926 | 9 军版要造谣，怎么都可以造。阿三要发文，还可以放Github。言论自由也保护他的个人
观点嘛。
现在谣言这么多，还这么多人肯信，主要是知识和逻辑的教育完全不到位。很多人头衔
很高，思维水平很低。
补充：还有很多带任务的四有老人。。。
【在 t******g 的大作中提到】
: 显然很多不懂行的人把这个老印的文章当正式发表的科学论文了啊.
| H********g
发帖数: 43926 | 10 另外，发表的论文也不一定就比没发表的要强多少。现在是特殊时候，还按部就班地走
审查发表路线，如果真的有用的内容就耽误了。
【在 t******g 的大作中提到】
: 显然很多不懂行的人把这个老印的文章当正式发表的科学论文了啊.
| d*******y
发帖数: 2710 | 11 很多是无文化，无脑子，无良心，无下水的四无功友。
【在 H********g 的大作中提到】
: 军版要造谣，怎么都可以造。阿三要发文，还可以放Github。言论自由也保护他的个人
: 观点嘛。
: 现在谣言这么多，还这么多人肯信，主要是知识和逻辑的教育完全不到位。很多人头衔
: 很高，思维水平很低。
: 补充：还有很多带任务的四有老人。。。
|
|
