Overfitting and treatment of "small data" are among the most challenging problems in the machine learning (ML), when a relatively small data statistics size $T$ is not enough to provide a robust ML fit for a relatively large data feature dimension $D$. Deploying a massively-parallel ML analysis of generic classification problems for different $D$ and $T$, existence of statistically-significant linear overfitting barriers for common ML methods is demonstrated. For example, these results reveal that for a robust classification of bioinformatics-motivated generic problems with the Long Short-Term Memory deep learning classifier (LSTM) one needs in a best case a statistics $T$ that is at least 13.8 times larger then the feature dimension $D$. It is shown that this overfitting barrier can be breached at a $10^{-12}$ fraction of the computational cost by means of the entropy-optimal Scalable Probabilistic Approximations algorithm (eSPA), performing a joint solution of the entropy-optimal Bayesian network inference and feature space segmentation problems. Application of eSPA to experimental single cell RNA sequencing data exhibits a 30-fold classification performance boost when compared to standard bioinformatics tools - and a 7-fold boost when compared to the deep learning LSTM classifier.