A novel Human RNA ligase est.2023

The humility of genomics

Those who lack humility and discover fire are usually the first burn victims.

If there is one smoldering ‘on fire’ message from the recent torrent of sequencing horsepower, it’s that genomics, epi-genomics and epi-transcriptomics are far more complicated than we ever imagined back at the start of the Human Genome Project. This insta-firehose of sequencing bandwidth has enabled the evaluation of all RNA/DNA at a single cell level and in thousands of cells, all in parallel. Over 100,000 human genomes have been NGS sequenced since the first generation of NGS (454, SOLiD, Illumina) inflection point (2007) on this chart.

A second inflection point in 2016 is seen with the maturation of the long read sequencers at PacBio and Oxford Nanopore Technology (ONT). These platforms can phase genomes (untangle mother and father genomes when sequencing diploid cells) and treat every human genome like it’s a de novo assembly problem. They can find novel content unrelated to the original reference sequence.

The first generations of NGS sequencers were short read sequencers. They operate by mapping the 50-500bp reads back to a reference genome and looking for differences between your sample and the reference. If your sample has novel genes that are not in the reference genome, then those are mostly missed.

The original human reference genome was comprised of a pool of 20 volunteers but resulted in 70% of the genome being derived from one African American donor collected by RPCI in Buffalo NY. Those 100,000 genomes were sequenced on short read sequencers (50bp-500bp) and mapped back to this reference genome.

The newer longer read sequencers (10,000- 1Mb reads) do not need to rely on a reference genome but can instead build a hypothesis-free genome from each individual. This affords the discovery of novel content.

This became the bleeding edge thing to do in 2022. Once we knew the technology could treat every genome in a hypothesis free manner and was affordable enough, the game changed. 8% more genome (200 Million bases/3B) was revealed, 1956 more predicted genes with 99 of those predicted genes being protein coding.

Today the NHGRI has announced the completion of a 47 human ‘pangenome’ project. This is 47 diverse genomes sequenced Telomere to Telomere and properly phased with these new longer read sequencers. These are sequenced to a far better quality standard than the initial Human Genome project constructed with Sanger and BAC end sequencing. This is phased perfect hypothesis free genomes, all cross compared to each other from diverse genetics around the world.

A great achievement in which the woke mind virus will need to wet its beak. It doesn’t take long for CNN to spin the project into equity and inclusivity story. You recall how much their promoted policies cared about starving the poor during the pandemic with lockdowns?

Remember when the essential versus non-essential business designation was oozing with equity and intensely inclusive?

Did they defend the nurses who acquired immunity but lost their jobs because they didn’t need nor want an experimental jab?

Hero to Zero is equity in the virtue starved, attention deficit disorder woke mind virus. Hijacking scientific achievements to cough out more cacophonies of communism, tempts me to put Katie Hunts name into an anagram generator.

It’s not that I’m against equity and inclusivity. It’s that the people most frequently hijacking these bromides actively engage in discrimination to achieve it.

Even with all of these exciting sequencing developments, we are still discovering the functionality of some of the esoteric genes discovered 2 decades ago. Our process of reading DNA far outstrips our capacity to understand what it means. Many genes in the human genome are homeless. They might appear as random logging coordinates in Maine to the unfamiliar eye.

You’ll recognize them with the acronym Open Reading Frame (ORF) in their name and a chromosome name (C12 = chromosome 12). This particular C12orf29 was discovered in 2003 in a large full length cDNA cataloging project in Japan. Two decades pass with this gene remaining in the realm of mystery.

Until Yuan et al.

At first glance, you might think.. Ehh.. Just another enzyme that modifies nucleic acids. No Biggie.

Not so fast.

Enzymes like this have not been found in vertebrates. This is major discovery and underscores how little we truly understand about RNA processing in the cell.

Its a beautiful paper that even knocks out the gene to see if its lethal.. Nope.

Cells can survive without it but once you raise ROS in the cell (Reactive Oxygen Species) such as what happens with an immune response, your RNA breaks down more readily. This human RNA ligase comes in to repair some of that damage. So people with LOF mutations in this gene might be very susceptible transcriptomic dysregulation during infection.

What does this mean?

We just injected billions of people with modified RNA and only afterwords discovered a major human RNA ligase that we were blind to before injection.

It’s like placing the lives of billions of people in the hands of a newly developed computer code, hitting run.. and then realizing the computer has a chip in it you didn’t know about that shuffles code.

We do not know how these RNA modification in the mRNA vaccines will interact with this newly discovered RNA Ligase. Will it concatenate them? Will the cell turn the modRNA into miRNAs and then RNA Ligases join miRNAs into longer pieces with different RNAi footprints?

The honest answer, is we don’t know and are committed to painfully finding out.

This precautionary position of mine on the genomics of the vaccine is often met with outrage as ‘spreading vax’ hesitancy. The moment one persons anxiety demands another person to require experimental injections, we have lost the plot.

Isn’t it interesting how the precautionary principle is always selectively invoked to advance incomprehensible political goals?

As a particularly grotesque example, this week ‘The Real Truther’ twitter space (that is openly hostile to skeptics of the covid narrative) decided it was time to shop my home address around as a veiled threat. This something I anticipated after publishing vaccine contamination.

When one of them was cornered for not understanding the biodistribution study they were professing to school physicians on (in a different Steve Kirsch space).. they resorted to ‘slap you around’ threats of violence and Doxx threats.

Their narrative is crumbling. The vax program is now being seen as a global Tuskegee trial turbo charged with vacuous social media influencers and Dunning Kruger like direct to consumer marketing. A social media influencer known as the alias ‘Drew’ even bragged about convincing over a 1 million people to get jabbed. He has no MD and believes his TikTok status is more relevant than a physicians opinion.

“Talk to your Doctor but then go get the vaccine” he states. As if your physicians visit is mundane passport stamp in the process of getting your holy water.

The consolidation of physicians into bureaucracies has eviscerated their voice and shamed them into herd medicine, while pharma funded or ideologically driven ‘influencers’ peddle medicine without a license. And this TikTok medicine is served with the slandering of the actual competent professionals in the field.

https://twitter.com/Kevin_McKernan/status/1656391995860873217?s=20

It was very good to hear Dr. Das put the focus back on the personalized medicine mantra and centered on the physician patient relationship. You can watch the social media influencers smoke screen of biobabble dissolve in minutes of debate with Dr. Das.

Well done sir.

It’s a long Twitter space. I have not listened to it all but 2hr:30mins in it starts to get interesting with Dr. Das.

https://twitter.com/Kevin_McKernan/status/1655891213675819011?s=20