A fully scalable online pre-processing algorithm for short oligonucleotide microarray atlases

Rapid accumulation of large and standardized microarray data collections is opening up novel opportunities for holistic characterization of genome function. The limited scalability of current preprocessing techniques has, however, formed a bottleneck for full utilization of these data resources. Although short oligonucleotide arrays constitute a major source of genome-wide profiling data, scalable probe-level techniques have been available only for few platforms based on pre-calculated probe effects from restricted reference training sets. To overcome these key limitations, we introduce a fully scalable online-learning algorithm for probe-level analysis and pre-processing of large microarray atlases involving tens of thousands of arrays. In contrast to the alternatives, our algorithm scales up linearly with respect to sample size and is applicable to all short oligonucleotide platforms. The model can use the most comprehensive data collections available to date to pinpoint individual probes affected by noise and biases, providing tools to guide array design and quality control. This is the only available algorithm that can learn probe-level parameters based on sequential hyperparameter updates at small consecutive batches of data, thus circumventing the extensive memory requirements of the standard approaches and opening up novel opportunities to take full advantage of contemporary microarray collections.