Author: Mengmeng

Continuing the topics about COVID-19 in the past two days, please let me talk about some co-evolution stuff. By the way, I stole today’s title from the program of SMBE 2020.

Host and pathogen always co-evolve to enable survival and flourish. There is a general idea: If the pathogen is “smart” enough, they will not kill all the hosts otherwise pathogen will lose their “habitats” and die out, too. Following this line of thinking, a “super smart” virus should increase its transmissibility and decrease its virulence so that it can have enough hosts to enable its reproduction. Sadly, COVID-19 is such a “super smart” virus.

Suppose I can get the COVID-19 samples from human tissues in different places, I would like to sequence the mixed DNA and separate them to human and COVID-19 sequences. Run genetic divergence analyses within human and virus to find out the candidate genes then pair the candidate genes if they were sampled together. The outstanding gene pairs may be associated with the specificity of virus strains and their hosts.

Yesterday, I presented some ideas about analyzing the spatial distribution of genetic variation in virus strains. Today, I am going to present some ideas on analyzing the genetic variations of virus over time, or to say, demographic history of virus. In doing so, we can understand the evolution of virus and identify some key genes associated with increased transmissibility and virulence.

First, window-based nucleotide diversity, Tajima’s D, Dxy and Fst analyses. Display these values along chromosomes as line plot and we may locate genomic regions showing distinctions.

Second, effective population size changes. Using PSMC and Dadi modelling methods, we can infer the changes of effective population size amongst different virus strains.

Third, gene birth and death analyses. We can use CAFE to analyze gene family evolution amongst virus strains. Then we can compare the enriched genes among the expansion and contraction families.

Fourth, detect positive selection markers. This step is the continuation of the first step. Along with some outgroup virus species, we can align orthologous genes, then run PAML to identify positive selection markers.

Taken together, we can use the above methods to detect, locate, pinpoint and understand some key genes which emerge in evolutionary process. These genes may be associated with increased transmissibility and virulence in host-pathogen interaction.

The geographic origin of COVID-19 is a hot topic on social media. Rumours, disinformation, unfounded conspiracy theories about this virus run wildly, which is fuelled by some political calculations. Media and public love this kind of frightening news rather than rational analyses — one weakness of humanity.

From a scientific perspective, the sequences of virus and genomics tools can provide us some clues. I have to emphasize at the beginning : We are tracing the origin not to blame on anyone, any country or any animal. We can use knowledge of geographic origin to better understand this virus — How this virus distribute in the world? Is there feature in its genome to help them quickly adapt to the local environment?

In this post, I present some analyses that can be performed to understand the geographic distribution of the virus. Supposedly, I can collect the virus samples from different places of the word, then genotype them by sequencing and acquire array of genetic variants: SNPs, copy number variations and INDELS.

First, genetic structure analyses. Cluster the strains from different places using PCA and Baysian clustering methods. Moving forward, construct phylogenetic trees to cluster these strains.

Second, isolation by distance and environment. Conduct linear regression of genetic differentiation (Fst) on geographic distance and environmental factors.

Third, GIS-based distribution analyses. Using non-linear regression methods such as spatial distribution modelling methods to associate the occurrence of different virus strains with climate/geographic factors.

Fourth, landscape genetics analyses. Associate genetic variants with climate/geographic factors using GWAS and outlier methods.

Taken together, the above methods can help us understand the spatial distribution of the virus, and genes underlying adaptation of these virus.

Mark today! Because today is February 29, 2020. We have Feb. 29 once in every four years. The calendar is actually a complicated system.

On such a special day, the below report made me laugh loudly — A view, in my opinion, belongs to “uneducated crudity and superficiality of naive thinking” .

Any control of pandemic relies on the responsive mechanism of medical care system and government management. For COVID-19, which has no effective treatment and vaccine until now, a harsh quarantine strategy has been proved to be the most effective means to prevent more infection. One dangerous clinical characteristics of COVID-19 is half of the infected patients don’t have fever or other obvious symptoms at the beginning of infection. The average transmission rate of COVID-19 is 2~3, which means one infected patient can transmit 2~3 healthy people. In this case, the contact tracing and “harsh response” as said in the above article help the patient acquire timely treatment, protect the medical-care workers, and most importantly, prevent more public infection. Chinese government put people’s lives at the first place. What’s more important than life? Authors of the above article may argue freedom is more important than life. This is the reason why I commented this view belongs to “uneducated crudity and superficiality of naive thinking”. Freedom doesn’t equal to private interests. If one person’s freedom may endanger the health and safety of peers, then this freedom must be constrained. In this case, I think other countries should take same actions as China to manage the ongoing or potential outbreak.

I seriously hope author of the above article and public take COVID-19 seriously. A popular view in western nations is the death rate is not high (about 2%), so COVID-19 can be regarded as flu. Death caused by COVID-19 occurs most in elder and people with preexisting conditions. In an ethical society, any life should be valued and respected. It is similar as taking flu vaccine. From a point of population immunity, injecting flu shot is not only protecting yourself but also the people surrounding you, especially those with a low immune function. A vigorous young man may not show severe symptoms in case being infected by flu virus, but the active virus may take lives of those who happen to contact this young man.

As of today, the COVID-19 has been spreading in South Korea, Japan, Italy, Iran and many other countries. More than 3000 confirmed cases were reported in South Korea. Super-spreaders occur in Italy and South Korea. What makes things worse is the virus strains in Iran and South Korea are different from strains discovered in China. This means this virus can mutate and from the severity of infection in Iran and South Korea, the mutation increase the virus transmissibility. COVID-19 outbreak tortures the medical system and causes panic amongst public. Fighting against virus is actually a war which needs the unity of all nations’ efforts. Any political leverage that put benefits above people’s lives is anti-human.

Again, happy leap day and fight against virus.

I was struck by this sentence today — ” What experience and history teaches us is that people and governments have never learned anything from history, or acted on principles deduced from it.” — by George Hegel (1770-1831). No wonder this saying goes “History is always surprisingly similar.” That’s because humans constantly repeated the past mistakes. As repetitive mistakes are unavoidable, do we have remedy strategies and correction system to mitigate the loss? While at least, we humans have realized and reflected on our stupidity, and start to think of that, thanks to Hegel. Isn’t this a progress of humanity ?

“Happiness rests upon individuality — inner constitution. ” By Arther Schopenhauer. Ecstasy is not happiness, because it can’t last long. An ailing man can’t feel happiness due to a poor quality of physique. I think the most important elements for a man being happy include: good health, sanguine personality, and meaningful career.

Why did I start blogging? Because I want to record my course of thoughts. I’ve been interested in a Hong Kong movie star’s blog recently. He started blogging from 2006, and since then, he posted one blog every day, writing about his ideas or activities within a short paragraph or two. He said he used the blog as a channel to communicate with his fans. Reading his 14 years’ blogs, I can see his transition — he has been growing up from an impulsive young guy to a mature, level-headed, and considerate man. Now, besides the huge fortune and fame made from acting work, this movie star has earned an incredibly widespread respect and compliment due to his charity work and services in HK actors’ association.

Inspired by him, I’ve decided to start blogging, recording my course of thought. I intend to write something that strike my mind during day, probably what I read or what I run into at work.

I’ve been so disappointed with social media which transmit a large amount of fake news and rumors. That’s why I post blogs in my personal website.

No one can predict future. But we can recall the past. I don’t expect I will be as famous and rich as that movie star, but at least, I hope to see the value of my life after 10 or more years. What kind of legacy I can leave to the world?

I borrowed this title from Alain de Botton’s book “Art as therapy”. He advocates in the book “Novels of Jane Austen, paintings of Titian and Botticelli, poetry of Matthew Arnold, can fill in the gap of departure of religion.” “Museums and galleries can be new Cathedrals.”

I believe in the healing power of art. I have experienced a hard time feeling sorrow and loss every day. After a month’s sleeplessness, I fianlly found comfort and calm in an adult Ballet class. I’ve been grateful that dance and music dragged me out of endless painful emotion.

During 2019 Evolution Meeting, I spent a couple of hours in RISD museum to appreciate some 18-18 Century landscape paintings, my favourite genre. During that short while, I felt like being in the Garden of Eden — time stops, happiness is eternal, no pain, no trouble, only peace and harmony.

I pursue the plesant and pretty aspects of art, and I reject the art reflecting the darkness of society. Regarding this, I think I can’t be an objective art critics, because I have such a preference and inclination in art.

I heard about this place during a random chat with my colleagues.  It is a 11 meters cliff located in South west Alberta where aboriginal people had been hunting buffalo for 5500 years. This is basically a hunting trick: Buffalos were driven to a lane by human-dressed-up coyotes and wolves.  Then at full gallop, the buffalos would fall from the weight of the herd pressing behind them, breaking their legs and rendering them immobile.   

I doubted the story at the beginning: why the behind buffalos did not stop running when they observed the front-line buffalos fell?    Today, I did a little research. I think the reason is the behind buffalos were forced by other buffalos to jump, even they did not want to.

This made me think of the importance of thinking independently.  “Follow your heart but with your brain”. Do not blindly follow others, even they are authorities.  I’ve seen many people trying to follow the “mainstream norm” to make sure they are on the right track. However, each individual is different. What suits others may not work on me.  We have to be level-minded and understand what really suit us in a certain situation.    

Now, another question arises:  Do we really understand ourselves? Do we know what we want?

I’ve given a lot of thoughts on science, art and humanity recently, thanks to this damn COVID-19. I’ve always been confident about the power of science. However, the outbreak and risk of Coronavirus make me realize science and technology are not solutions to any problem.  Human beings still suffer from pain, loss, disease and disaster. At this time, only art, beauty of nature and religious faith can bring a little comfort and peace to the sufferers.