all individuals gave informed consent for inclusion before they participated in the study. human lung tissues were procured under each institution ’ s approved irb protocol ( numbers 00035396 ( cedars - sinai medical center ), 03 - 1396 ( university of north carolina at chapel hill ), 1172286 ( cystic fibrosis foundation and wirb - copernicus group western irb ) and 16 - 000742 ( university of california, los angeles ) ). informed consent was obtained from lung donors or their authorized representatives. the study was approved and monitored by the national jewish health irb ( fwa00000778 ). written informed consent was obtained from all participants. the study protocol was approved by the partners healthcare irb ( protocol 2011p002419 ). lung tissue was obtained under a protocol approved by the university of pittsburgh irb ( irb study 19100326 ) during transplantation surgery. the study was conducted according to the principles expressed in the declaration of helsinki. ethical approval was obtained from ethics committee research uz / ku leuven ( s63881 ). all participants provided written informed consent for sample collection and subsequent analyses. approval was given by the nres committee of east of england — cambridge south ( 15 / ee / 0152 ). the cbtm operates in accordance with uk human tissue authority guidelines. samples were obtained from deceased transplant organ donors by the cbtm with informed consent from the donor families. ethical approval was given through the living airway biobank, administered through the university college london great ormond street institute of child health ( rec reference: 19 / nw / 0171; integrated research application system ( iras ) project id: 261511; north west liverpool east rec ), rec reference 18 / sc / 0514 ( iras project id: 245471; south central hampshire b rec; administered through the university college london hospitals nhs foundation trust ), rec reference 18 / ee / 0150 ( iras project id: 236570; east of england — cambridge central rec; administered through great ormond street hospital nhs foundation trust ) and rec reference 08 / h0308 / 267 ( administered through the cambridge university hospitals nhs foundation trust ), as well as by the local r & d departments at all hospitals. all of the study participants or their surrogates provided informed consent. all protocols were reviewed and approved by the irb at the memorial sloan kettering cancer center ( irb protocol 14 - 091 ). noninvolved lung, tumor tissues and metastatic lesions were obtained from patients with lung adenocarcinoma undergoing resection surgery at the memorial sloan kettering cancer center after obtaining informed consent. samples underwent irb review and approval at the institutions where they were originally collected. specifically, the dana - farber cancer institute approved protocol 13 - 416, the partners massachusetts general hospital and brigham and women ’ s hospital approved protocols 2020p000804, 2020p000849 and 2015p002215, the beth israel deaconess medical center approved protocols 2020p000406 and 2020p000418 and new york presbyterian hospital / columbia university irving medical center approved protocols irb - aaat0785, irb - aaab2667 and irb - aaas7370. secondary analysis of samples at the broad institute was covered under massachusetts institute of technology irb protocols 1603505962 and 1612793224, or the not human subjects research protocol orsp - 3635. donor identities were encoded at the hospitals before shipping to or sharing with the broad institute for sample processing or data analysis, respectively. the study was approved by the local ethics committee of the ludwig maximilian university of munich ( ek 333 - 10 and 382 - 10 ). written informed consent was obtained from all patients. for schiller _ 2021 ( h. b. s., j. g. - s., c. h. m., b. h. k., m. a. et al., newly generated dataset ), the study was approved by the local ethics committee of the ludwig maximilian university of munich ( ek 333 - 10 and 382 - 10 ). written informed consent was obtained from all patients. for schultze _ unpubl ( j. l. s., c. s. f., t. s. k. and e. c., newly generated dataset ), human lung tissue was available for research purposes following ethical approval from hannover medical school ( ethical vote of the german centre for lung research ( dzl ) number 7414, 2017 ). all patients in this study provided written informed consent for sample collection and data analysis. samples were obtained under the cells and mediators irb protocol ( 2003p002088 ). all individuals provided written informed consent. the studies described were conducted according to the principles of the declaration of helsinki. the study was approved by the university of california, san francisco irb. written informed consent was obtained from all individuals. peripheral blood was obtained from healthy consenting adult volunteers by venipuncture through a protocol approved by the columbia university irb. all relevant ethical regulations for work with human participants were complied with. donor lung samples were provided through the federal united network for organ sharing via the national disease research interchange and international institute for the advancement of medicine and entered into the nhlbi lungmap brindl at the university of rochester medical center, overseen by the irb as rsrb00047606. for for the pooled data from ref. and associated unpublished data, human lung tissue collection was approved by the duke university irb ( pro00082379 ) and university of north carolina biomedical irb ( 03 - 1396 ) under exempt protocols. consent was obtained to use human tissues for research purposes. the study was approved by the local ethics committee at university hospitals leuven ( b322201422081 ) and all of the relevant ethical regulations were complied with. only patients with untreated, primary, nonmetastatic lung tumors who underwent lung lobe resection with curative intent and who provided informed consent were included in this study. all of the research involving human participants was approved by the northwestern university irb. samples from patients with covid - 19, viral pneumonia and other pneumonia, as well as controls without pneumonia, were collected from participants enrolled in the successful clinical response in pneumonia therapy study stu00204868. all study participants or their surrogates provided informed consent. the irb of the university of cincinnati college of medicine approved all human - relevant studies. the study was conducted according to the principles expressed in the declaration of helsinki. ethical approval was obtained from the rec of shenzhen third people ’ s hospital ( 2020 - 112 ). all participants provided written informed consent for sample collection and subsequent analyses. further study details can be found in supplementary table 1. several previously unpublished datasets were used for the hlca and generated as follows. participants recruited by the pneumology unit of nice university hospital were sampled between 1 and 15 december 2020. the full procedure, including patient inclusion criteria, is detailed at https: / / www. clinicaltrials. gov / ct2 / show / nct04529993. nasal and tracheobronchial samples were collected from patients with ipf after obtaining their informed consent, following a protocol approved by the centre hospitalier universitaire de nice. the data were derived from the clinical trial registered at clinicaltrials. gov under reference nct04529993. this study was described as an interventional study instead of an observational study because the participants were volunteers and all assigned to a specific bronchoscopy not related to routine medical care. participants were prospectively assigned to a procedure ( bronchoscopy ) according to a specific protocol to assess our ability to sample the airway. no other procedures were included in this study. metadata of the donors ’ sex was based on self - report.