Methods, systems, and devices are disclosed for processing macromolecule sequencing data with substantial noise reduction. In one aspect, a method for reducing noise in a sequential measurement of a macromolecule comprising serial subunits includes cross-correlating multiple measured signals of a physical property of subunits of interest of the macromolecule, the multiple measured signals including the time data associated with the measurement of the signal, to remove or at least reduce signal noise that is not in the same frequency and in phase with the systematic signal contribution of the measured signals.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
 This invention was made with government support under grant DE-AC52-06NA25396 awarded by the U.S. Department of Energy (DOE), along with grant FA9550-10-1-0409, awarded by the Air Force Office of Scientific Research (AFOSR), and along with grant HG002647 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.