A viral exposure signature (VES) that can identify early stage, pre-symptomatic hepatocellular carcinoma (HCC) among at-risk patients is described. The VES was developed using serological profiling and synthetic virome technology to identify unique viral peptide epitopes corresponding to 61 viral species. Methods of identifying a subject with early stage (pre-symptomatic) HCC using the VES are described.

Improved compositions and methods for using modified non-retroviral reverse transcriptase to perform 3′ extension of a nucleic acid, employ non-templated deoxynucleotide addition to a single-stranded nucleic acid and/or synthesis of complementary DNA using non-complementary nucleic acids as primer and template (RNA- or DNA-templated DNA polymerase activity.

Provided are a separator for separating a nucleic acid amplification system, comprising a polyethylene wax, a solid paraffin wax, and a liquid paraffin wax. Also provided is a method for separating a nucleic acid amplification system, comprising using the separator as a separation layer to separate a nucleic acid amplification system within a same container. The separating layer can be broken by means of applying an external force, thereby mixing the nucleic acid amplification system.

The current invention provides methods of combinatorial genetic screening in a cancer cell comprising an enhanced CRISPR-Cas12a system, and compositions comprising the same. Also provided are methods for screening for synergistic combinations of drug targets, as well as the treatment of cancer in a subject in need thereof.

Characterization of the binding dynamics at the interface between any two proteins that specifically interact plays a role in myriad biomedical applications. The methods disclosed herein provide for the high-throughput characterization of the specific interaction at the interface between two protein binding partners and the identification of functionally significant mutations of one or both protein binding partners. For example, the methods disclosed herein may be useful for epitope and paratope mapping of an antibody-antigen pair, which is useful for the discovery and development of novel therapies, vaccines, diagnostics, among other biomedical applications.

The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

Disclosed herein are insulin resistance reporters for use in quantifying insulin response in biological cells. These biological cells may be stem cell compositions or derivatives thereof comprising the insulin resistance reporter. The stem cell derivatives include but are not limited to insulin responsive cells, tissues, or organoids, such as pancreatic, brain, adipose, muscle, or liver cells, or tissues or organoids thereof. Also disclosed herein are methods of using said insulin resistance reporters and cells with these insulin resistance reporters as models to examine insulin resistance and screening for compounds that are potentially useful for the treatment of diseases or disorders associated with insulin resistance. The cells comprising an insulin resistance reporter may be hepatic cells or liver organoid compositions, which can be used in investigating hepatic insulin resistance, for example, as a result of non-alcoholic fatty liver disease or steatohepatitis.

An object of the present invention is to provide a method for producing a non-ribosomal RNA-containing sample, which comprises a novel step for removing ribosomes. According to the present invention, there is provided a method for producing a non-ribosomal RNA-containing sample, which comprises the step (a) of splitting subunits of ribosomes and mRNAs in a sample containing mRNAs and ribosomes, and the step (b) of removing the subunits of ribosomes split in the step (a).

The invention is directed to modified oligonucleotide compositions and methods for selectively reducing unwanted nucleic acid contaminants and enriching for desired nucleic acid targets from complex genomic nucleic acid mixtures for sequencing applications. The modified oligonucleotide compositions include one or more modified groups that increase the T.sub.m of the resultant oligonucleotide composition.

The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.