Abstract: The present disclosure relates to compositions and methods for nucleic acid sequencing, and specifically, at least in certain aspects, provides methods and compositions for enhancing the efficacy, throughput and/or yield of known long-range sequencing platforms, by providing chimeric arrays of input sequences. Such arrays of component nucleic acid sequence elements can be prepared via methods that minimize introduction of bias. The application of the current methods to obtain isoform sequencing information, e.g., from patient samples is specifically also provided, as are methods for mitochondrial lineage tracing that employ the instant chimeric amplicon sequencing processes. Methods and systems for array nucleic acid sequence processing and interpretation are also provided.

Abstract: This disclosure provides methods and systems for single-extracellular (EV), multi-omic analysis of target EVs without microfluidic devices. The disclosed methods involve the use of template particles to template the formation of monodisperse droplets to generally capture a single target EV from a population of EVs in an encapsulation, derive a plurality of distinct mRNA molecules from the single target EV, and quantify the distinct mRNA molecules to generate an expression profile. Nucleic-acid-tagged antibody conjugates are used for simultaneous proteomic analysis along with the gene expression profiling, which enables classification of an EV in a sample.

Abstract: A way to design a codebook for estimating the type of a molecule at a particular location in a fluorescence microscopy image makes use of one or both of (1) knowledge of the non-uniform prior distribution of molecule types (i.e., some types are known a priori to occur more frequently than others) and/or knowledge of co-occurrence of molecule types at close locations (e.g., in a same cell); and (2) knowledge of a model of the (e.g., random) process that yields the intensities that are expected at a location when a molecule with a particular subset of markers (i.e., a molecule of a type that has been assigned a codeword that defines that subset) is present at that location. The codebook design may provide experimental efficiency by reducing the number of images that need to be acquired and/or improve classification or detection accuracy by making the codewords for different molecule types more distinctive.