Provided herein are compositions, devices, systems and methods for the generation and use of biomolecule-based information for storage. Additionally, devices described herein for de novo synthesis of nucleic acids encoding information related to the original source information may be rigid or flexible material. Further described herein are highly efficient methods for long term data storage with 100% accuracy in the retention of information. Also provided herein are methods and systems for efficient transfer of preselected polynucleotides from a storage structure for reading stored information.

Processes and materials to detect cancer from a biopsy are described. In some cases, cell-free nucleic acids can be sequenced, and the sequencing result can be utilized to detect sequences derived from a neoplasm. Detection of somatic variants occurring in phase can indicate the presence of cancer in a diagnostic scan and a clinical intervention can be performed.

Nucleic acid molecule comprising a coding sequence and a region of increased folding energy upstream of a stop codon are provided. Expression vectors and cells comprising the nucleic acid molecule are also provided. Methods for optimizing a coding sequence comprising increasing folding energy in a region upstream of the stop codon are also provided.

The present disclosure provides methods for optimizing barcode design for multiplex DNA sequencing. Also disclosed are DNA barcodes optimized for use with particular sequencing technologies.

The present disclosure provides methods of identifying source organisms for antibiotic agents and methods of producing novel antibiotic agents. In particular, the disclosure provides methods of identifying novel source organisms for antibiotic agents by sing functionally significant structural motifs to select probes, and mining genome sequences using the selected probes to identify suitable source organisms for production and isolation of novel antibiotic agents.

Systems, media, methods, and kits disclosed herein can improve analysis capabilities of genomic materials. Results from such analyses can be used to detect genomic biomarkers in one or more genomic materials. The systems, media, methods and kits disclosed herein can identify changes or patterns among samples, and can employ machine learning methods to explore changes or potential changes in biological conditions or risks thereof. Further, the systems, media, methods and kits disclosed herein can utilize machine learning algorithms to analyze samples with high accuracy.

Provided herein are systems and methods for screening desirable biological variants using a high-throughput integrated system. The integrated system may be configured to input a plurality of parameters from functional studies of biological variants under applied conditions, in conjunction with integrated libraries of biological variants, and filter the inputs to produce desirable biological variants based on an input performance requirement. The system may output optimized strains, molecules, or novel molecules expected to have a desirable functional characteristic. Accordingly, the methods and systems disclosed herein enable multi-parametric studies of biological diversity and conditional diversity in systems biology.

The present invention is directed to a chimeric polypeptide including a polypeptide of interest N-terminal to an essential protein of a target cell. Further provided is a polynucleotide encoding the chimeric polypeptide, a method of producing thereof, and a method for producing a protein of interest. The chimeric polypeptide of the invention improves the genetic stability of the polypeptide of interest ensuring its expression over time.

The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the installation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

Provided herein are compositions, devices, systems and methods for the generation and use of biomolecule-based information for storage. Additionally, devices described herein for de novo synthesis of nucleic acids encoding information related to the original source information may be rigid or flexible material. Further described herein are highly efficient methods for long term data storage with 100% accuracy in the retention of information. Also provided herein are methods and systems for efficient transfer of preselected polynucleotides from a storage structure for reading stored information.