Integrating massively parallel sequencing into diagnostic workflows and managing the annotation and clinical interpretation challenge.

Massively parallel sequencing has become a powerful tool for the clinical management of patients with applications in diagnosis, guidance of treatment, prediction of drug response, and carrier screening. A considerable challenge for the clinical implementation of these technologies is the management of the vast amount of sequence data generated, in particular the annotation and clinical interpretation of genomic variants. Here, we describe annotation steps that can be automated and common strategies employed for variant prioritization.

A comparison of molecular and cytogenetic techniques for the diagnosis of pregnancy loss.

Purpose: To evaluate the sensitivity, specificity, advantages, and limitations of multiplex ligation-dependent probe amplification compared with conventional karyotype analysis in the investigation of contributing factors to recurrent pregnancy loss.

Method: A cohort of 284 patients underwent side-by-side analysis of products of conception by both conventional karyotyping and multiplex ligation-dependent probe amplification with direct comparison of results.

Results: Multiplex ligation-dependent probe amplification was shown to enable a diagnosis for an additional 47 (16.