The host response to viral infections is a critical determinant for severe disease pathogenesis. Interdisciplinary approaches such as omics technologies, high-throughput screening, high content imaging, next generation sequencing (NGS), and computational biology have provided a deeper understanding of the molecular mechanisms underlying disease pathogenesis, promising to accelerate the development of therapeutics and vaccines. However, the lack of reproducibility due to inconsistencies in experimental methods and models, variability in big data analysis methods and heterogeneity in biological systems may also misguide our understanding of the critical host responses that mediate viral pathogenesis and protection. The goal of this Methods Collection is to standardise protocols describing high-throughput data generation, including methods for RNA sequencing, NGS, microarray, mass spectrometry, high-content imaging, single cell sequencing, deep immunophenotyping, mitochondria characterization and metabolomics, with particular emphasis on the protocol steps that ensure consistency and reliability in data. We also welcome methods on bioinformatic approaches that facilitate big data analysis, omics data analysis, systems biology research and image processing.