Deep #mutational #scanning of #H5 #hemagglutinin to inform #influenza virus #surveillance, BioRxIV: https://www.biorxiv.org/content/10.1101/2024.05.23.595634v2
Here we use pseudovirus deep mutational scanning to measure how all mutations to a clade 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind a2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA.
#Phylogenetic & #mutational #analysis of #H10N3 avian #influenza A virus in #China: potential #threats to #human #health, Front Cell Infect Microbiol.: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1433661/full
Analysis of aa mutation sites identified 4 mutations potentially hazardous to human health. Consequently, this underscores importance of continuous & vigilant monitoring of dynamics surrounding H10N3 subtype of avian influenza virus, utilizing advanced #genomic surveillance techniques.
Deep #mutational #scanning of #H5 #hemagglutinin to inform #influenza virus #surveillance, BioRxIV, https://www.biorxiv.org/content/10.1101/2024.05.23.595634v1
Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.
Deep #mutational #scanning of #influenza A virus #NEP reveals pleiotropic #mutations in its N-terminal domain http://biorxiv.org/cgi/content/short/2024.05.16.594574v1?rss=1
The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation.
Author summary SARS-CoV-2 variants evolve in part via mutations in the spike receptor-binding domain (RBD) that impact the ability of this domain to evade binding by neutralizing antibodies while maintaining high-affinity binding to ACE2 receptor. To aid in ongoing viral forecasting and surveillance, we conducted high-throughput measurements of the impacts of all possible amino acid mutations or single-codon deletions on ACE2 binding in the newly evolved Omicron BQ.1.1 and XBB.1.5 variant backgrounds. We find that mutations and deletions are well-tolerated in these domains, consistent with the ongoing evolutionary potential of Omicron sub-variants. We show that the impacts of mutations on ACE2 binding continue to change over time due to the phenomenon of epistasis, though these shifts in mutational effect are less pronounced than epistatic shifts described in earlier variants of concern. Nonetheless, we show that this epistasis continues to enable SARS-CoV-2’s exploration of new mutational combinations as it evolves into new regions of sequence space, highlighting the ongoing evolutionary potential this virus will continue to exhibit.
#Plants' ingenious defense against #mutational damage.
#segregation #agriculture #oDNA #genomics
https://phys.org/news/2023-11-ingenious-defense-mutational.html
Humans wouldn't last long without plant mitochondria and chloroplasts. These essential compartments of plant cells famously capture sunlight and power plant life—and so, ultimately, provide all the food we eat. But there's a problem: Mitochondria and chloroplasts store instructions for their building blocks in their own "organelle" DNA or oDNA—and this can get mutated.
The influential American number theorist Leonard Dickson wrote 'Thank God that number theory is unsullied by any application.'
And yet, again and again, number theory finds unexpected applications in science and engineering, from leaf angles that (almost) universally follow the Fibonacci sequence, to modern encryption techniques based on factoring prime numbers.
Now, researchers have demonstrated an unexpected link between number theory and evolutionary genetics.
Specifically, the team of researchers - from Oxford, Harvard, Cambridge, GUST, MIT, Imperial, and the Alan Turing Institute - have discovered a deep connection between the sums-of-digits function of number theory and a key quantity in genetics: #phenotype #mutational #robustness.
This quality is defined as the average probability that a point mutation does not change a phenotype (a characteristic of an organism).
They proved that the maximum robustness is proportional to the logarithm of the fraction of all possible sequences that map to a phenotype, with a correction which is given by the sums of digits function sk(n), defined as the sum of the digits of a natural number n in base k. For example, for n = 123 in base 10, the digit sum would be s10(123) = 1 + 2 + 3 = 6.
Another surprise was that the maximum robustness also turns out to be related to the famous Tagaki function, a bizarre function that is continuous everywhere, but differentiable nowhere.
First author Dr. Vaibhav Mohanty (Harvard Medical School) added: 'What is most surprising is that we found clear evidence in the mapping from sequences to RNA secondary structures that nature in some cases achieves the exact maximum robustness bound. It's as if biology knows about the fractal sums-of-digits function.'
https://www.news-medical.net/news/20230808/Unexpected-link-between-pure-mathematics-and-genetics-discovered.aspx
An interdisciplinary team of mathematicians, engineers, physicists, and medical scientists have uncovered an unexpected link between pure mathematics and genetics, that reveals key insights into the structure of neutral mutations and the evolution of organisms.
Deep #mutational scanning of essential bacterial proteins can guide #antibiotic development |
#amr #geneticscreens
https://www.nature.com/articles/s41467-023-35940-3
Deep mutational scanning can be used to investigate protein function and stability. Here, Dewachter et al. use deep mutational scanning on three essential bacterial proteins to study the mutations’ effects in their original genomic context, providing insight into the proteins’ function and their potential as targets for new antibiotic development.
How can we tell how different #cancer cells will respond to various drugs? 💊
ERC grantee @FranSupek @IRBBarcelona found out that the answer lies in the “#mutational signature” left on the entire cancer genome.
More? ➡️ https://bit.ly/3o3Xydr #CancerResearch
@GenomeDataLab
🐦🔗: https://nitter.eu/ERC_Research/status/1552194603498909697
Giuseppe Michieli
CellBioNews
Chuck Darwin
Vivek Mutalik
European Research Council (ERC