Advances in spatial proteomics: Mapping proteome architecture from protein complexes to subcellular localizations.

Proteins are responsible for most intracellular functions, which they perform as part of higher-order molecular complexes, located within defined subcellular niches. Localization is both dynamic and context specific and mislocalization underlies a multitude of diseases. It is thus vital to be able to measure the components of higher-order protein complexes and their subcellular location dynamically in order to fully understand cell biological processes. Here, we review the current range of highly complementary approaches that determine the subcellular organization of the proteome. We discuss the scale and resolution at which these approaches are best employed and the caveats that should be taken into consideration when applying them. We also look to the future and emerging technologies that are paving the way for a more comprehensive understanding of the functional roles of protein isoforms, which is essential for unraveling the complexities of cell biology and the development of disease treatments.

Direct costs of interferon-based and interferon-free direct-acting antiviral regimens for the treatment of chronic hepatitis C infection.

Given the increasing budget impact of Hepatitis C virus (HCV) treatment, robust real-world cost data are essential for healthcare decision-makers to evaluate and understand the costs and benefits of these treatments. To determine the direct cost of treating HCV infection in a hospital-based ambulatory care setting in Ireland based on available data from the Irish national hepatitis C treatment registry. A microcosting study of the direct costs of patients with hepatitis C treated with interferon-based and interferon-free direct-acting antiviral regimens was conducted. Attendance at the outpatient clinic for clinical assessment, the quantity of resources used per patient, the medication prescribed and the identification and timing of staff involvement was measured and combined to establish a mean cost of treatment per patient and a cost per sustained virological response (SVR). One hundred and sixty-eight patients were included in the analysis; 119 treated with interferon-based direct-acting antiviral regimens and 47 treated with interferon-free regimens. The mean costs of treatment with the interferon-based regimens per patient were €38 286 (95% CI €35 305-€41 061). The cost per SVR was €62 457. The mean cost of treatment with interferon-free regimens per patient was €55 734 (95% CI €50 906-€60 880). The cost per SVR was €81 873. Real-world cost data provide valuable information to enhance reimbursement decisions. While the direct costs associated with hepatitis C treatment in Ireland are substantial, it is reasonable to expect that the mean cost of treatment and the cost per SVR will reduce as patients with less advanced disease are treated with interferon-free therapies.