Abstract: The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.

Abstract: Methods for predicting the outcome of production of peptides are provided, as well as methods for producing peptides or providing products comprising peptides, which uses said methods. The methods comprise providing a primary amino acid sequence for one or more peptides, and Provide ore or more metrics predicting the outcome of production of the one or more peptides by chemical synthesis using a machine learning model that has been trained to predict one or more metrics characterising the outcome of production of peptides using training data comprising training peptide primary sequences and measured metrics characterising the outcome of production of the training peptides by chemical synthesis. The measured metrics are metrics obtained after completion of the chemical synthesis process. Systems and products for performing the methods are also described.

Abstract: The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.

Abstract: Exemplary embodiments include a system to prevent flow of data or cross-contamination from a higher level classification system to a lower level classification system. A cross domain guard allows a data or network connection between processors handling data of different classification levels. The cross domain guard may allow for uni-directional or bi-directional data flow. The guard may allow flow of data from the lower level to the higher level. A normalization server may be used to allow for exchange and/or input and/or processing of data or material from different sources. The normalization server receives an input from a source (e.g., a platform, a payload, a system, open source, etc.). The input data may be a particular format. The normalization server may perform any required data conversion.

Abstract: The present disclosure provides compositions and methods related to analyzing DNA, such as cell-free DNA. In some embodiments, the cell-free DNA is from a subject having or suspected of having cancer and/or the cell-free DNA includes DNA from cancer cells. In some embodiments, the DNA is partitioned into a first subsample and a second subsample, wherein the first subsample comprises DNA with a nucleotide modification (e.g., a cytosine modification) in a greater proportion than the second subsample, and the second subsample is subjected to a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the first subsample, and the DNA is sequenced in a manner that distinguishes the first nucleobase from the second nucleobase in the DNA of the second subsample.

Abstract: Exemplary embodiments include a system to prevent flow of data or cross-contamination from a higher level classification system to a lower level classification system. A cross domain guard allows a data or network connection between processors handling data of different classification levels. The cross domain guard may allow for uni-directional or bi-directional data flow. The guard may allow flow of data from the lower level to the higher level. A normalization server may be used to allow for exchange and/or input and/or processing of data or material from different sources. The normalization server receives an input from a source (e.g., a platform, a payload, a system, open source, etc.). The input data may be a particular format. The normalization server may perform any required data conversion.

Abstract: Genomic library preparation using Cas-gRNA RNPs, and targeted epigenetic assays, are provided herein. Some compositions include, from a first species, substantially only single-stranded polynucleotides; from a second species, substantially only double-stranded polynucleotides; and amplification primers ligated to ends of the second double-stranded polynucleotides and substantially not ligated to any ends of the first double-stranded polynucleotides. Some compositions include first and second molecules of a target polynucleotide having a sequence, the first molecule having a first end at a first subsequence, the second molecule having a first end at a second subsequence, wherein the first subsequence only partially overlaps with the second subsequence. Some examples provide a composition that includes a target polynucleotide and a first fusion protein including a Cas-gRNA RNP coupled to a transposase having an amplification adapter coupled thereto.

Abstract: Disclosed herein include systems and methods for designing probes for depleting abundant transcripts from a sample. Abundant sequence reads can be determined in a species-agnostic manner, and probes for depleting abundant transcripts can be designed based on the sequences of the top abundant sequences. Also disclosed herein include compositions and kits for depleting abundant transcripts and methods for depleting abundant transcripts.

Abstract: The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.

Abstract: In an aspect, the present disclosure provides a method for determining a methylation status comprises: providing a biological sample of nucleic acid molecules; partitioning at least a subset of the nucleic acid molecules in the biological sample based on the methylation status of the nucleic acid molecules into a plurality of partitioned sets; digesting at least a subset of the one or more partitioned sets in the plurality of partitioned sets with at least one methylation sensitive restriction enzyme; enriching at least a subset of the nucleic acid molecules in the plurality of partitioned sets for genomic regions of interest, wherein the at least a subset of the nucleic acid molecules comprises digested nucleic acid molecules in the one or more partitioned sets; and determining methylation status at one or more genetic loci of the nucleic acid molecules in at least one of the partitioned sets.

Abstract: Sequencing nucleic acids can identify variations associated with presence, susceptibility or prognosis of disease. However, the value of such information can be compromised by errors introduced by or before the sequencing process including preparing nucleic acids for sequencing. Blunting single-stranded overhangs on nucleic acids in a sample can introduce deamination-induced sequencing errors. The disclosure provides methods of identifying and correcting for such deamination-induced sequencing errors and distinguishing them from real sequence variations.

Abstract: Disclosed herein are compositions and methods for isolating DNA, such as cell-free DNA (cfDNA). In some embodiments, the cell-free DNA is from a subject having or suspected of having cancer and/or the cell-free DNA comprises DNA produced by a tumor. In some embodiments, the DNA isolated by the method is captured using a sequence-variable target region set and an epigenetic target region set, wherein the sequence-variable target region set is captured with a greater capture yield than the epigenetic target region set. In some embodiments, captured cfDNA of the sequence-variable target region set is sequenced to a greater depth of sequencing than captured cfDNA of the epigenetic target region set.

Abstract: The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.

Abstract: Provided herein, in some embodiments, are cytosine analogs, compositions comprising cytosine analogs, and methods of use for inhibiting a Ten-eleven translocation (TET) enzyme.

Abstract: Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the sequencing library includes nucleic acids that represent the chromatin accessibility from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. In another embodiment, the present disclosure provides methods for characterizing rare events in isolated cells and nuclei.

Abstract: Methods of preparing double-stranded nucleic acids with single-stranded overhangs for amplification and sequencing are disclosed. Contacting a blunt-ended double-stranded nucleic acid molecules with Taq results in non-templated directed addition of a single nucleotide to the 3? ends of the nucleic acid with A added most frequently followed by G followed by C and T. G tailing is sufficiently frequent that the efficiency of ligation of nucleic acid molecules to adapters can be significantly increased by including adapters tailed with T and C. The ligation efficiency can be increased even further with blunted-ended adapters to ligate to blunt-ended nucleic acid molecules that failed to undergo tailing.

Abstract: The present disclosure is directed to a bicycle parking structure comprising a plurality of bicycle hangers supported by a crossbar assembly. Each bicycle hanger is configured to support a bicycle in a substantially vertical position. The bicycle hangers are spaced apart from one another along the length of the crossbar assembly. Each of the bicycle hangers may be secured to the crossbar assembly so that the bicycle hanger is fixed at a desired position or unsecured from the crossbar assembly so that the position of the bicycle hanger along the length of the crossbar assembly may be adjusted. In this manner, the distance between adjacent bicycles need not be fixed and the bicycle parking structure can be adapted for a particular space. The bicycle parking structure is designed to provide for a space-efficient, high-volume parking of bicycles.

Abstract: Disclosed herein include systems and methods for designing probes for depleting abundant transcripts from a sample. Abundant sequence reads can be determined in a species-agnostic manner, and probes for depleting abundant transcripts can be designed based on the sequences of the top abundant sequences. Also disclosed herein include compositions and kits for depleting abundant transcripts and methods for depleting abundant transcripts.