The Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ): A patient-reported, disease-specific measure.

Objectives: To assess the reliability and validity of age-specific versions of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ), developed to measure the impact of FOP on physical function and activities of daily living.

Methods: FOP-PFQ development included a literature review, two iterative phases of qualitative work involving individuals with FOP, and clinical expert review. The analysis used pooled FOP-PFQ data from an FOP natural history study (NCT02322255), a patient registry (NCT02745158), and phase II trials (NCT02190747; NCT02279095; NCT02979769).

Accurate assembly of minority viral haplotypes from next-generation sequencing through efficient noise reduction.

Rapidly evolving RNA viruses continuously produce minority haplotypes that can become dominant if they are drug-resistant or can better evade the immune system. Therefore, early detection and identification of minority viral haplotypes may help to promptly adjust the patient's treatment plan preventing potential disease complications. Minority haplotypes can be identified using next-generation sequencing, but sequencing noise hinders accurate identification.

Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel.

Purpose: To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.

Experimental Design: Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples.

Inference of genetic relatedness between viral quasispecies from sequencing data.

Background: RNA viruses such as HCV and HIV mutate at extremely high rates, and as a result, they exist in infected hosts as populations of genetically related variants. Recent advances in sequencing technologies make possible to identify such populations at great depth. In particular, these technologies provide new opportunities for inference of relatedness between viral samples, identification of transmission clusters and sources of infection, which are crucial tasks for viral outbreaks investigations.

Long Single-Molecule Reads Can Resolve the Complexity of the Influenza Virus Composed of Rare, Closely Related Mutant Variants.

As a result of a high rate of mutations and recombination events, an RNA-virus exists as a heterogeneous "swarm" of mutant variants. The long read length offered by single-molecule sequencing technologies allows each mutant variant to be sequenced in a single pass. However, high error rate limits the ability to reconstruct heterogeneous viral population composed of rare, related mutant variants.

Computational framework for next-generation sequencing of heterogeneous viral populations using combinatorial pooling.

Motivation: Next-generation sequencing (NGS) allows for analyzing a large number of viral sequences from infected patients, providing an opportunity to implement large-scale molecular surveillance of viral diseases. However, despite improvements in technology, traditional protocols for NGS of large numbers of samples are still highly cost and labor intensive. One of the possible cost-effective alternatives is combinatorial pooling.

Reconstruction of viral population structure from next-generation sequencing data using multicommodity flows.

Background: Highly mutable RNA viruses exist in infected hosts as heterogeneous populations of genetically close variants known as quasispecies. Next-generation sequencing (NGS) allows for analysing a large number of viral sequences from infected patients, presenting a novel opportunity for studying the structure of a viral population and understanding virus evolution, drug resistance and immune escape. Accurate reconstruction of genetic composition of intra-host viral populations involves assembling the NGS short reads into whole-genome sequences and estimating frequencies of individual viral variants.