Human Pangenomics: Promises and Challenges of a Distributed Genomic Reference

Abstract

A pangenome is a collection of the common and unique genomes that are present in a given species. It combines the genetic information of all the genomes sampled, resulting in a large and diverse range of genetic material. Pangenomic analysis offers several advantages compared to traditional genomic research. For example, a pangenome is not bound by the physical constraints of a single genome, so it can capture more genetic variability. Thanks to the introduction of the concept of pangenome, it is possible to use exceedingly detailed sequence data to study the evolutionary history of two different species, or how populations within a species differ genetically. In the wake of the Human Pangenome Project, this review aims at discussing the advantages of the pangenome around human genetic variation, which are then framed around how pangenomic data can inform population genetics, phylogenetics, and public health policy by providing insights into the genetic basis of diseases or determining personalized treatments, targeting the specific genetic profile of an individual. Moreover, technical limitations, ethical concerns, and legal considerations are discussed.

GWAS advancements to investigate disease associations and biological mechanisms

“…84,85 The Pangenome's concept demonstrates a promising strategy to surmount the limitations of GWAS stemming from the traditional reliance on a singular linear reference genome, such as GRCh38 assembly, NCBI Build 37 (hg19), African Reference Genome (AR1), and reference panels such as those from the 1KG and the HRC. 87,88 This approach involves assembling a collection of individual haploid genome sequences that represent the genetic diversity of a population or species 88 and encompassing both the core genome, which is shared among all individuals, and the accessory genome, which is specific to certain individuals or subgroups. 88 This facilitates the identification of novel genetic associations.…”

“…87,88 This approach involves assembling a collection of individual haploid genome sequences that represent the genetic diversity of a population or species 88 and encompassing both the core genome, which is shared among all individuals, and the accessory genome, which is specific to certain individuals or subgroups. 88 This facilitates the identification of novel genetic associations. 89 Pangenome's analysis has significantly lowered false mapping rates, improved allelic bias and enhanced the accuracy of gene expression analysis compared to conventional linear reference pipelines such as STAR 90 or VG MPMAP.…”

Proyecto genoma veinte años después: el primer 'pangenoma humano'

“…Las ventajas de trabajar con el pangenoma estriban en que se puede detectar más variabilidad genética al no limitarse a un solo genoma; es posible estudiar la historia evolutiva de la especie; y se da más claridad sobre la base genética de determinadas enfermedades, para diseñar tratamientos más personalizados, al tener en cuenta el perfil genético de cada enfermo (7). Todo esto redundará en mejores conocimientos sobre la genética de las poblaciones, la medicina forense y, sobre todo, la llamada medicina personalizada.…”