Statistical processing of Flash X-ray Imaging of protein complexes

Flash X-ray Imaging (FXI) at X-ray Free Electron Lasers (XFELs) is a promising technique that permits the investigation of the 3D structure of molecules without the need for crystallization, by diffracting on single individual sample particles. In the past few years, some success has been achieved by using FXI on quite large biological complexes (40 nm-1 μm in diameter size). Still, the desired dream-goal of imaging a single individual of a molecule or a protein complex (<15 nm in diameter size) has not been reached yet. The main issue that prevented us from a complete success has been the low signal strength, almost comparable to background noise. That is particularly true for experiments performed at the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). In this thesis, we provide a brief review of the CXI instrument (focusing on experiments there performed) and present a statistical method to deal with low signal-to-noise ratios. We take into account a variety of biological particles, showing the benefits of estimating a background model from sample data and using that for processing said data. Moreover, we present the results of some computer simulations in order to explore the limits and potentials of the proposed approach. Last, we show another method (named COACS) that, being fed with the previous findings from the background model, helps obtaining clearer results in the phase retrieval problem