Integrated genomics refers to the use of large-scale, systematically collected data from various sources to address biological and biomedical problems. A critical ingredient to a successful research program in integrated genomics is the establishment of an effective computational infrastructure. In this review, we suggest that the computational infrastructure challenges include developing tools for heterogeneous data organization and access, innovating techniques for combining the results of different analyses, and establishing a theoretical framework for integrating biological and quantitative models. For each of the three areas - data integration, analyses integration, and model integration - we review some of the current progress and suggest new topics of research. We argue that the primary computational challenges lie in developing sound theoretical foundations for understanding the genome rather than simply the development of algorithms and programs.
Computational Biology ; Foundations ; Genome ; Genomics*

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
Animals ; Mice ; Neurons ; Proprioception ; Gene Expression Profiling ; Pain ; Sequence Analysis, RNA