A Network Approach Improves Diagnosis of Rare Diseases

Even though rare genetic diseases are usually caused by a mutation to a single gene, a new study finds examining a patient’s biology at multiple levels increases the ability to discern the specific genetic cause underlying a patient’s condition.

For the study, published in Nature, scientists at the Research Center for Molecular Medicine of the Austrian Academy of Sciences built a multilayer network, mapping more than 20 million gene relationships with information ranging from protein interactions to phenotypic similarities. In all, they organized it into 46 network layers spanning six major biological scales between genotype and phenotype. To do this, they integrated a comprehensive dataset of more than 3,700 rare diseases with a known genetic basis.

“The multiplex network integrates different network layers that map different levels of the biological organization of our body, from the genome to the transcriptome, proteome and phenotype,” said Jörg Menche, one of the paper’s authors. “By mapping protein interactions and mechanisms, we can also better characterize those proteins whose roles in disease were previously unknown and thus track down gene defects more efficiently.”

The researchers said that the network approach increases the probability of finding the crucial gene aberration threefold compared to when these networks are considered separately. The modular design makes it possible to quantify the impact of a particular rare disease on a specific level of biological organization. This means determining whether certain cells, tissues, or organs are particularly affected by a genetic defect.

At the same time, the importance of certain molecular processes for a disease can also be measured. That makes it easier to make predictions about the possible consequences of the genetic defect.

“Our study shows how a huge dataset can be used in the context of network medicine to address several practical and conceptual challenges in rare disease research to improve diagnosis and treatment for the benefit of patients,” said Menche.

Author: Rare Daily Staff