Mycobacterium tuberculosis is the most common pathogenic agent responsible for tuberculosis (TB) infection. Over a period of time, the methods used for combating TB have become more challenging by the prevalence of multi-drug resistant and extensively drug resistant strains. The disclosure relates generally to method and system for combating infections due to Mycobacterium tuberculosis. The system provides strategies to combat pathogenic infections caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis. The strategy involves identifying potential target sites in a pathogen, which can be utilized to compromise its multiple virulence or essential functions at the same time. The present disclosure utilizes the fact that a conserved stretch of nucleotide repeat sequence occurring multiple times on a pathogen genome in genomic neighborhood of genes encoding virulence factors for pathogen survival can be targeted to disrupt the overall genetic machinery of the pathogen.

Fluorophores are used during the synthesis of oligonucleotides to achieve real-time quality control of the synthesis process. Fluorescence may indicate successful addition of individual nucleotides to a growing oligonucleotide strand or removal of a blocking group. The oligonucleotides may be created by enzymatic synthesis using terminal deoxynucleotidyl transferase (TdT). The synthesis is performed on an addressable array so that oligonucleotides with different sequences are created in parallel on different regions of the array. The oligonucleotide sequences are predetermined and the locations of synthesis on the array are controlled. Observed fluorescence is compared to expected locations of fluorescence as determined by the oligonucleotide sequences and the arrangement on the array. Thus, the fidelity of oligonucleotide synthesis is checked as synthesis proceeds. If a variation is found, a mitigating action is taken such as repeating addition of a species of nucleotide or repeating a deblocking step.

Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a target region, which is typically located within one or more target fragments. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations.

Provided herein are compositions and methods for identifying genomic variants. Further provided herein are standards useful for determining the analytical sensitivity and/or accuracy of instruments configured to measure nucleic acid variant frequencies.

Provided herein are compositions and methods for identifying genomic variants. Further provided herein are standards useful for determining the analytical sensitivity and/or accuracy of instruments configured to measure nucleic acid variant frequencies.

Described herein are solid supports and methods for depleting library fragments prepared from unwanted RNA sequences and/or enriching library fragments prepared from desired RNA sequences. These methods may incorporate microfluidics and flowcells for greater ease of use. Libraries enriched or depleted with the present methods may be used for sequencing. Also described are probes and methods for enzymatic depletion of ribosomal RNA from human microbiome samples.

A method for developing capture agents for target proteins employs a compound library to find cyclic peptide sequences that bind the target protein. The target protein is also reacted with a clickable group-provider reagent to provide the protein with clickable groups. The compounds in the library are provided with complementary clickable groups that bind the clickable group on the target protein when the peptide sequences bind the target protein. In some embodiments, the cyclic peptide sequences that bind the target protein are incorporated into constructs having one or more arms that can serve as capture agents or potential treatments against the pathogens from which the target protein is derived. Some embodiments provide pharmaceutical compositions for immunoassays, diagnostics, therapeutics or the like, that employ the constructs.

The present invention discloses a profiling technique for a target molecule population in a sample including an unknown target molecule, using an aptamer. In the method of the present invention, the target molecule population in the sample may be provided as an aptamer profile including an unknown target molecule, and this aptamer profile can be used to determine whether drug prescription is appropriate (i.e., anticancer drug companion diagnosis, etc.), to provide disease diagnosis information, to monitor drug treatment, to determine drug compliance, to determine the degree or absence/presence of in vitro cellular response to drug treatment, and to obtain useful information to humans for classification or identification of species, etc.

The purpose of the present invention is to provide a method of producing a library including two or more cyclic peptides, wherein at least one of the cyclic peptides included in the library has a structure composed of 4 to 30 amino acids or derivatives thereof and contains, in the structure, at least one selected from cyclic β-, γ-, and δ-amino acids (cAAs), including a step of preparing an mRNA library encoding a peptide having a sequence represented by the formula (1); —(Xaa).sub.n1- [in the formula (1), Xaas are each an arbitrary amino acid or derivative thereof, at least one Xaa is one selected from cyclic β-, γ-, and δ-amino acids (cAAs) and n1 is an integer of 2 to 28] and a step of using the mRNA library to express the peptide in a cell-free translation system and produce a library.

Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence αXβ, wherein X is the desired peptide epitope, wherein each of α and β comprise an amino acid, using the peptide library to select an affinity reagent.