Machine Learning Analysis of the Bleomycin Mouse Model Reveals the Compartmental and Temporal Inflammatory Pulmonary Fingerprint

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  1. ###Reviewer #2:

    The manuscript lacks a clear hypothesis/message. It is ultimately descriptive and adds very little to our understanding of the role of immune mechanisms in the development of tissue fibrosis (including pulmonary fibrosis). Detailed profiling of the immune populations in the context of the bleomycin-induced fibrosis model has been reported previously (Tighe et al., AJRCMB, 2011, PMID 21330464). Similarly, results of the spatial analysis are also not surprising: the authors used the lung injury model and found an accumulation of the recruited immune cells in the areas of injury/fibrosis. Moreover, spatial methods are lacking appropriate rigor necessary for quantitative assessment (i.e. stereology, see Hsia et al., AJRCCM, 2010, PMID 20130146). As a machine learning methods paper, it also lacks novelty (several dimensionality reduction techniques plus random forest classifier) and not validated using external datasets.

  2. ###Reviewer #1:

    This paper uses multiple approaches to study the cellular dynamics of murine bleomycin lung injury as a model for human IPF. Multiple techniques are used for this purpose including multi-parameter flow, histology, data reduction technique, comparative analysis between BAL and lung, non-linear mixed modeling and immunohistochemistry. The results are interesting and propose a staged inflammatory response leading to IPF like pathology. However, the data is very descriptive and does not test a specific hypothesis. In particular, the results do not suggest a particular therapeutic strategy. Addition of a targeted intervention to the experiments would enhance the impact of the work.

  3. ##Preprint Review

    This preprint was reviewed using eLife’s Preprint Review service, which provides public peer reviews of manuscripts posted on bioRxiv for the benefit of the authors, readers, potential readers, and others interested in our assessment of the work. This review applies only to version 1 of the manuscript.

    ###Summary:

    The manuscript uses a large temporal immuno-phenotyping dataset in the broncho-alveolar fluid and lungs of mice given bleomycin, so as to enable the modelling of the localised progression from innate to adaptive inflammation and subsequent fibrosis. While this is an immense amount of work and the analysis is interesting, the concerns regarding rigor in spatial quantification and the primarily descriptive nature of the work make the resultant insights, mechanistic or translational, somewhat too limited for a cross-disciplinary readership.