Sequencing data have been deposited at the European Genome-Phenome Archive (http://www.ebi.ac.uk/ega/) under accession numbers EGAD00001005193. Somatic mutation calls, including single base substitutions, indels and structural variants, from all 632 samples have been deposited on Mendeley Data with the identifier: http://dx.doi.org/10.17632/b53h2kwpyy.2. Code Availability Detailed method and custom R scripts for the analysis of mutational burden in bronchial epithelium are available in Supplementary Code. Other packages used in the analysis are listed below:

The electromagnetic ͑EM͒ enhancement in surface-enhanced resonance Raman scattering ͑SERRS͒ is quantitatively evaluated for rhodamine molecules adsorbed on Ag nanostructures. Polarization dependence of the plasma resonance ͑plasmon resonance͒ and the SERRS spectra from single isolated Ag nanostructures was evaluated to determine one-to-one relationship between optical anisotropy of plasma resonance, that of SERRS, and the morphology of the nanostructures. Experimental observations were compared with finitedifference time-domain calculations of the EM field induced by plasma resonance using individual morphology of the nanostructures. The experimental enhancement factor of SERRS ϳ10 9 was consistent with that of the calculations within a factor of ϳ2 for three excitation wavelengths. We conclusively fortify the indispensible importance of SERRS-EM theory with our results to design metal nanostructures generating strong EM enhancement.

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We analyze blinking in surface enhanced resonance Raman scattering (SERRS) and surface enhanced fluorescence (SEF) of rhodamine 6G molecules as intensity and spectral instability by electromagnetic (EM) mechanism. We find that irradiation of intense NIR laser pulses induces blinking in SERRS and SEF. Thanks to the finding, we systematically analyze SERRS and SEF from stable to unstable using single Ag nanoparticle (NP) dimers. The analysis reveals two physical insights into blinking as follows. (1) The intensity instability is inversely proportional to the enhancement factors of decay rate of molecules. The estimation using the proportionality suggests that separation of the molecules from Ag NP surfaces is several angstroms. (2) The spectral instability is induced by blueshifts in EM enhancement factors, which have spectral shapes similar to the plasmon resonance. This analysis provides us with a quantitative picture for intensity and spectral instability in SERRS and SEF within the framework of EM mechanism.