Sunday, June 21, 2020

Xinfadi SARS-CoV-2 strains closer to East Asian or European; contaminated salmon is from Chile

Writer : Tang Bohu
Editor : Kongwen Zhan
Publisher :  Ifeng News, edited on 6parknews.com
Extract translation, editing by : Gan Yung Chyan
                                                / KUCINTA SETIA

According to Phoenix TV news anchor writer Tang Bohu, through an alternative gene sequencing method through bioinformatics known as Nextstrain, it appears that the Xinfadi Market strains of SARS-CoV-2 appear closer to East Asian strains. Using the GISAID method, they appear closer to European strains. Besides, the contaminated salmon at Xinfadi Market originates from Chile, and not Norway. The following edited text is the extract translation of Bohu's Chinese essay.

Details about Nextstrain

Ordinary people must find GISAID professional virus sequences completely incomprehensible.

Therefore, a team of virus evolution experts such as Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle, USA, organized a project called Nextstrain.

The Nextstrain project seeks to analyze gene sequence changes through bioinformatics. Putting different viruses together to see which virus mutates more, the more changes are generally the viruses that have evolved and updated, and the less mutations are closer to the original virus.

This analysis pays particular attention to the specific points of change, for example, a sample has a change G-T at the 20000th point.

Then, if the new samples collected afterwards also have G-T changes at the 20,000th point, it can be considered that they are all descendants of the previous virus.

Because according to probability, the probability of other novel coronaviruses also independently changing here is only 1 in 30,000.

The starting point of Nextstrain calculation is the first sample sequence (lower left corner) collected on Wuhan on December 24, 2019, and uploaded on January 11, 2020, and the earlier sequence. In actual calculation, there are far more changes. For example, a certain virus has specific mutations at the 15000th, 20000th, and 25000th points.

Then it is certain that the viruses with mutations in the 5000th and 15000, 20000, 25000, and 10000th and 15000, 20000, and 25000, and the same mutations in the last three loci must be the progeny of the previous virus.

The powerful analysis capabilities of bioinformatics on virus mutations gave birth to "genomic epidemiology", which can track the spread and evolution of viruses through the evolution of the entire genome sequence of the virus.

This is a very powerful tool, just like the application of gene sequencing and specific sites in criminal investigation.

Nextstrain not only automatically analyzes the virus transmission and evolution through algorithms, but also provides a visualized virus evolution tree through the website.

Therefore, it not only provides convenience for the general public and general biological researchers, but also is recognized and cooperated by GISAID.

What does the evolutionary tree of the virus tell us?

At Nextstrain, nearly 3000 virus sequences automatically presented the panorama of the new coronavirus pandemic.

According to the major mutation of the virus, people have divided the viruses so far into 19A, 19B, 20A, 20B, and 20C groups. The preceding number indicates the year of occurrence.


Legend above :
The 19 series, mainly spread in the Asia-Pacific region (blue in the picture), and partly spread to the west coast of the United States (red).

The 20 series began to be uploaded by scientists in late February, mainly spreading in Europe (orange), and partially spread to the east coast of the United States (red) and Latin America (orange).

There are also quite a few 20B and 20C series that return to Asia Pacific (blue) through international flights, the proportion is not small.


Legend above : Virus evolutionary transmission maps colored on all continents, blue Asia Pacific, cyan Oceania, green Africa, khaki Europe, orange yellow South America, red North America.

In the previous report, Beijing’s new virus sequencing was described as “from Europe”, and was later supplemented with a few sentences “but it’s a little different from the current European prevalence. It’s older than the European prevalence. ".

These summary terms are too vague and unpredictable.

But now the Chinese CDC has submitted the genome sequence of the new virus in Beijing to WHO and GISAID, so we can easily understand the position of the virus in the virus evolution tree.

Although it is believed that the new virus in Beijing belongs to the 20B cluster, the information released this time is slightly different from what was previously expected.

Is the Xinfadi SARS-CoV-2 strain from Taiwan?

With the virus sequence and Nextstrain, it is possible to locate the precise location of the Beijing new virus in the virus evolution tree.

The 20B cluster is positioned, and the Beijing new virus is in the upper right corner. Zoom in on the white area to get the picture below.

It is found that the white area in the above picture is still complicated after being enlarged.


The 20B cluster is positioned, and the Beijing new virus is in the upper right corner. Zoom in on the white area to get the picture below.

It is found that the white area in the above picture is still complicated after being enlarged.

Continue to enlarge the white area in the above picture to get the following picture.



Zoom in on the white (the new cluster of Beijing new virus) and the light grey (adjacent cluster) in the above picture to get the following picture.



Continue to zoom in on this new virus cluster in Beijing to get the picture below.



It turned out that the closest to Beijing's new virus was actually a Taiwanese sample on 17 March.

The virus sequence numbered "Taiwan/CGMH-CGU-13/2020" was collected and reported by the famous Chang Gung Memorial Hospital in Taoyuankou. The origin of the sample is unknown. 


So, many netizens exclaimed, "Is Taiwan poisoning?"

Another algorithm, another possibility

However, Nextstrain has different algorithms, and the virus database of income has also been adjusted. Under another algorithm, the result is quite different.

20B large cluster. Zoom in on the white (local cluster of Beijing new virus) and light gray (adjacent cluster) to get the following figure.

Zoom in on the white (the new cluster of Beijing new virus) and the light gray (adjacent cluster) in the above picture to get the following picture.


Those with closer kinship have become Denmark and the Czech Republic, and the virus detected in March in Taiwan is farther away.
 
Be aware that Nextstrain, as a public-facing visualization tool, is limited by performance and readability, and can only process about 3000 genomes in one view. Therefore, Nextstrain has been streamlining, adjusting the repeated and unimportant sequences in the database, and promptly collecting new important data (such as the newly released Beijing new virus) to keep all data below 2900.

GISAID currently has more than 49,000 viral gene sequences. In addition, according to the summary statistics of China National Microbiological Science Data Center, there are more than 1,000 sequence data in GenBank, and more than 50,000 viral genomes have been published worldwide.

Therefore, the inclusion rate of Nextstrain is only 5.8%. The 50,000 genome-wide data that has been published is a small percentage of the total number of 8.6 million nucleic acid diagnoses worldwide.


The current 4 possibilities

Therefore, when there is a lot of missing sequencing data, the viral genome sequence can only be roughly located, and it cannot be confirmed where the virus in Beijing came from.

But a professional bioinformatician, using the GISAID database (20 times the data), will surely be able to produce more accurate results than we use the Nextstrain automatic algorithm, but it will only take time.

However, no matter what algorithm it is, the novel coronavirus in Beijing has a high correlation with the virus sequence detected by Taiwan and the 20B reflux epidemic cluster in the Asia-Pacific region, followed by European countries such as Denmark, Czech Republic, and Portugal.

According to the scientific facts of the virus sequence by Nextstrain and the common social logic, it is possible to summarize the possible sources of the imported epidemic in Beijing. The possibilities are arranged in descending order:

1. The movement of people between East Asian countries and regions led to the Beijing epidemic.

Judging from the SARS-CoV-2 sequence, the new Beijing virus strain belongs to the 20B European cluster of return Asia-Pacific clusters, and is particularly related to the virus detected by Taiwan in March. This needs attention.

From the perspective of social logic, East Asian talents have the habit and demand to buy fresh food in huge new places.

Westerners stationed in Beijing shop at the characteristic farmer's market in Chaoyang District where foreigners live. Only here do they have the special ingredients and ingredients they need. Most of the food is very different.

Moreover, East Asians' shopping activities in Xinfadi are very unobtrusive, and it is difficult for the person concerned to recall them in later epidemiological investigations.

2. Chilean frozen salmon, a batch of which was contaminated by infected workers at the end of March. After being shipped to China and thawed, it caused the epidemic situation in Beijing Xinfadi and the Tianjin five-star hotel.

But only this batch, the others are virus-free, so other contaminated salmon in Beijing cannot be found.

3. People returning/entering from Europe caused an epidemic. There is less possibility.

4. The virus entered Russia via Suifenhe River in March and early April, and then spread to Beijing secretly.

This possibility is the least, because according to the results of gene sequencing, the SARS-CoV-2 strain in Beijing is not related to the coronavirus strain in Russia.

Viruses cannot be born out of nothing. If people are infected by viruses, they must have been in contact with a person or a thing carrying the virus, or have been to the environment where the virus exists.

Finally, everyone is reminded that against the background of the overwhelming majority of governments in the world, the world's epidemic and China's national defense control must continue until the mass production of vaccines.

During this "long period", maintaining one's own protective measures is still a must.



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