Deep learning in spatially resolved transcriptfomics: a comprehensive technical view

Spatially resolved transcriptomics (SRT) is a pioneering method for simultaneously studying morphological contexts and gene expression at single-cell precision. Data emerging from SRT are multifaceted, presenting researchers with intricate gene expression matrices, precise spatial details and comprehensive histology visuals. Such rich and intricate datasets, unfortunately, render many conventional methods like traditional machine learning and statistical models ineffective. The unique challenges posed by the specialized nature of SRT data have led the scientific community to explore more sophisticated analytical avenues. Recent trends indicate an increasing reliance on deep learning algorithms, especially in areas such as spatial clustering, identification of spatially variable genes and data alignment tasks. In this manuscript, we provide a rigorous critique of these advanced deep learning methodologies, probing into their merits, limitations and avenues for further refinement. Our in-depth analysis underscores that while the recent innovations in deep learning tailored for SRT have been promising, there remains a substantial potential for enhancement. A crucial area that demands attention is the development of models that can incorporate intricate biological nuances, such as phylogeny-aware processing or in-depth analysis of minuscule histology image segments. Furthermore, addressing challenges like the elimination of batch effects, perfecting data normalization techniques and countering the overdispersion and zero inflation patterns seen in gene expression is pivotal. To support the broader scientific community in their SRT endeavors, we have meticulously assembled a comprehensive directory of readily accessible SRT databases, hoping to serve as a foundation for future research initiatives.