TY - JOUR T1 - Logarithmic molecular sampling for next-generation sequencing JF - bioRxiv DO - 10.1101/420299 SP - 420299 AU - Caroline Horn AU - Julia Salzman Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/27/420299.abstract N2 - Next-generation sequencing enables measurement of chemical and biological signals at high throughput and falling cost. Conventional sequencing requires increasing sampling depth to improve signal to noise discrimination, a costly procedure that is also impossible when biological material is limiting. We introduce a new general sampling theory, Molecular Entropy encodinG (MEG), which uses biophysical principles to functionally encode molecular abundance before sampling. SeQUential DepletIon and enriCHment (SQUICH) is a specific example of MEG that, in theory and simulation, enables sampling at a logarithmic or better rate to achieve the same precision as attained with conventional sequencing. In proof-of-principle experiments, SQUICH reduces sequencing depth by a factor of 10. MEG is a general solution to a fundamental problem in molecular sampling and enables a new generation of efficient, precise molecular measurement at logarithmic or better sampling depth. ER -