Rare Does Not Mean Worthless: How Rare Diseases Have Shaped Neurodevelopment Research in the NGS Era

Abstract

The advent of next-generation sequencing (NGS) is heavily changing both the diagnosis of human conditions and basic biological research. It is now possible to dig deep inside the genome of hundreds of thousands or even millions of people and find both common and rare genomic variants and to perform detailed phenotypic characterizations of both physiological organs and experimental models. Recent years have seen the introduction of multiple techniques using NGS to profile transcription, DNA and chromatin modifications, protein binding, etc., that are now allowing us to profile cells in bulk or even at a single-cell level. Although rare and ultra-rare diseases only affect a few people, each of these diseases represent scholarly cases from which a great deal can be learned about the pathological and physiological function of genes, pathways, and mechanisms. Therefore, for rare diseases, state-of-the-art investigations using NGS have double valence: their genomic cause (new variants) and the characterize the underlining the mechanisms associated with them (discovery of gene function) can be found. In a non-exhaustive manner, this review will outline the main usage of NGS-based techniques for the diagnosis and characterization of neurodevelopmental disorders (NDDs), under whose umbrella many rare and ultra-rare diseases fall.

Automatic Classification and Visualization of Text Data on Rare Diseases

“…The purpose of this analysis is threefold: first, we need to establish some understanding of the data; second, we will have very limited expert annotation time, and we must make sure we select a viable pool of candidates, e.g., if the number of articles we can find about a rare disease is too small, it might be a bad candidate; thirdly, presenting this analysis provides data to substantiate the need for an automated text classifier to help identify articles related to rare diseases. We are aware of more than 7000 rare diseases, with around 5000 classified as neurodevelopmental disorders (NDDs), which are typical examples of rare diseases [14]. These NDDs often share overlapping features and clinical symptoms, allowing for collective analysis and study to a certain extent.…”