here is the Pangenome that will make it possible to create tailor-made treatments – breaking latest news

We used to imagine DNA as the great book of life, the code to decipher ourselves, the Rosetta stone of humanity, the operating manual of Homo sapiens. But the repertoire of metaphors deserves to be updated. Today our species portrait has taken on the appearance of a network made up of knots and relationships. Welcome to theepoch of the pangenome: the overall genome (pan in Greek means everything) which aims to gradually become more complex, plural, cosmopolitan and inclusive.

Paradigm leap

The Human Pangenome Project is an initiative promoted by the American National Institutes of Health which today lands in the scientific journal Nature with three original works, and su Nature Biotecnology with a fourth study. Among the creators is the Italian bioinformatician Giulio Formenti, who we asked to explain to us what this paradigm shift consists of. After the draft of the genome in 2001, the complete genome of 2003 arrived which was not so complete, then last year it was the turn of the T2T genome sequenced from end to end (from telomere to telomere), and now here is the pangenome . Must we free ourselves from the logic of the finish line to cross? Yes, we have to think of it as a work in progress, the last transition just starting, says al Courier this 35-year-old talent who teaches at Rockefeller University in New York.

Technologies make the difference

Let’s try to understand what distinguishes the latest discovery from the pompous announcement of the standard sequence at the time of the Clinton presidency. The Human Genome Project had been working on a handful of samples donated by volunteers, whose recruitment had taken place in Buffalo with an ad placed in a local newspaper. All the sequences obtained subsequently were compared with that patchwork genome, considered standard even if it was far from representing the world. The pioneer of the study of human genetic differences was Luigi Luca Cavalli-Sforza, in a sense the pangenome collects its legacy by ferrying it to the time of precision sequences and super-assembly algorithms says the scientist originally from Milan. This is one of those cases where technologies make the difference, because enormous computing power is needed to catalog and annotate, letter by letter, sequence by sequence, everything that changes from one individual to another, from one population to another. other.

For sequences, quality is also important

If we unravel the double helix, DNA is a string of letters, linear and one-dimensional, but a set of human genetic variations must be stratified, must acquire depth. How did it? In jargon we say that a graph. In practice a network whose nodes represent the regions of sequence shared between the genomes and the divergent regions. The structure of the data allows you to analyze them in an innovative way, observe how the variations are distributed and make new discoveries.
For now, the pangenome contains only 94 genomes, belonging to 47 people (each of us has two different copies). It may seem little, since there are projects from many thousands of genomes. But for the pangenome perfect sequences are needed, quality as well as quantity is important, explains Formenti. Another peculiarity concerns the updates to be made as new data arrives: each time the pangenome must be reworked from scratch. The third difficulty concerns the medical community that will have to learn to compare patients’ DNA with a graph instead of a simple reference sequence. This will take time, but it is worth it, because in this way it will be possible to evaluate each individual variation and create tailor-made treatments, for example in the oncological field.

Crossroads of migrations

By mid-2024, the pangenome will contain 700 genomes belonging to 350 people and the consortium is discussing which criteria to follow in sample selection. Italy will be represented thanks to samples sequenced at the Human Technopole by Alessandro Raveane and by researchers from the Center for Medical and Population Genomics directed by Nicole Soranzo in collaboration with the University of Florence. Our country has been a crossroads of migrations, therefore it presents a great variability, let’s think for example of Tuscans and Sardinians. well it is included in the pangenome for everyone’s benefit says Formenti. As the pangenome becomes more inclusive it will be a better mirror in which to look at and recognize ourselves as a species. What image will it return? Today in the books it is written that we are all 99.9% equal, these percentages will have to be recalculated. We will find confirmation of the fact that there are no races understood as rigid and separate categoriesand human diversity will be higher than that documented so far.