Abstract: Provided herein are devices, methods, and systems for next-generation volumetric in situ sequencing of nucleic acids in cells in intact tissue. In particular, methods are provided for improving robustness across sample types, including for thin and thick tissue volumes, and increasing the efficiency and specificity of target labeling for volumetric combinatorial in situ sequencing.

Abstract: Provided herein are devices, methods, and systems for multiple feature integration with next-generation three-dimensional in situ sequencing of nucleic acids in cells in intact tissue. Biological samples contain many distinct types of molecular, cellular, anatomical, and experimental features. The disclosed methods allow simultaneous interrogation of multiple distinct features of a biological sample, including RNA features, anatomical features, exogenous barcodes, or other arbitrary experimental features such as in vivo measurements, which can be combined into single experimental readouts with next-generation in situ sequencing.

Abstract: Sequencing chemistries and encodings for in situ gene sequencing are provided. Next-generation DNA sequencing and in situ sequencing techniques are dependent on robust, accurate, and efficient read out chemistries and encodings. The sequencing chemistries and encodings provided herein can be used with any commercial sequencing service in which sequencing readout is required. These chemistries and encodings may also be used for non-sequenced detection of target nucleic acids, multiplexed in situ labeling, and various applications in pathology and histology.

Abstract: Methods, systems, and devices, including computer programs encoded on a computer storage medium are provided for processing of next-generation in situ sequencing data for nucleic acids in cells in tissue. In particular, cloud-based scalable data processing software for volumetric in situ sequencing is provided.

Abstract: A sequencer for automated in situ sequencing of volumetric tissue samples is provided. In particular, an automated volumetric in situ sequencing device capable of operating on multiple samples in parallel is provided. Methods of fabrication and use of the sequencer are also provided.

Abstract: Methods of modulating dissociative and associative states in a subject are provided. In particular, neuromodulation of rhythmic neural activity in the posteromedial cortex can be used to induce or inhibit dissociative states in a subject.

Abstract: Provided herein are devices, methods, and systems for in situ gene sequencing of a target nucleic acid in a cell in an intact tissue. Methods of screening a candidate agent to determine whether the candidate agent modulates gene expression of a nucleic acid in a cell in an intact tissue are also provided herein.