Disclosed are a rigorous method and apparatuses for the comprehensive analysis of complex mixtures of organic molecules, specifically biopolymers, in some embodiments predominantly mixtures of proteins, which in some embodiments ultimately serve to obtain the information constituting a biomarker, or similar biological signature, or to monitor health or ageing.

In some embodiments such signatures or patterns may indicate the presence, stage, or type of a disease, the expected or actual response to drugs. In some other embodiments such a method and apparatuses may serve to monitor and/or control cell development. In some other embodiments such a method and apparatuses may serve to develop and use means to measure, influence, or control the speed or degree of aging of cells or organisms.

In some embodiments such a method and apparatuses may serve to determine at least in part the nature of biological hazards, bioterrorism threats, or biological weapons, including those based on bacteria and viruses. In some embodiments such a method and apparatuses may serve to select, develop, and or optimize countermeasures to biological hazards, bioterrorism threats, or biological weapons, including those based on bacteria and viruses.

In other embodiments such a method and apparatuses may be used to asses the expected performance level of a human or animal for a specific task or for a class or problems.

Disclosed are a rigorous method and apparatuses for the comprehensive analysis of complex mixtures of organic molecules, specifically biopolymers, in some embodiments predominantly mixtures of proteins, which in some embodiments ultimately serve to obtain the information constituting a biomarker, or similar biological signature, or to monitor health or ageing.

In some embodiments such signatures or patterns may indicate the presence, stage, or type of a disease, the expected or actual response to drugs. In some other embodiments such a method and apparatuses may serve to monitor and/or control cell development. In some other embodiments such a method and apparatuses may serve to develop and use means to measure, influence, or control the speed or degree of aging of cells or organisms.

In some embodiments such a method and apparatuses may serve to determine at least in part the nature of biological hazards, bioterrorism threats, or biological weapons, including those based on bacteria and viruses. In some embodiments such a method and apparatuses may serve to select, develop, and or optimize countermeasures to biological hazards, bioterrorism threats, or biological weapons, including those based on bacteria and viruses.

In other embodiments such a method and apparatuses may be used to asses the expected performance level of a human or animal for a specific task or for a class or problems.

MALDI-MS operated slightly under matrix storm conditions with a high-energy-transfer, acidic matrix, or these conditions with a high sample to matrix ratio, can with ultrasensitivity detect a nucleobase, modified or canonical, of a nucleic acid species as a jettisoned, protonated molecule.

MALDI-MS operated slightly under matrix storm conditions with a high-energy-transfer, acidic matrix, or these conditions with a high sample to matrix ratio, can with ultrasensitivity detect a nucleobase, modified or canonical, of a nucleic acid species as a jettisoned, protonated molecule.

Methods are provided for detecting the amount of one or more CAH panel analytes (i.e., pregnenolone, 17-OH pregnenolone, progesterone, 17-OH progesterone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, deoxycorticosterone, 11-deoxycortisol, and cortisol) in a sample by mass spectrometry. The methods generally involve ionizing one or more CAH panel analytes in a sample and quantifying the generated ions to determine the amount of one or more CAH panel analytes in the sample. In methods where amounts of multiple CAH panel analytes are detected, the amounts of multiple analytes are detected in the same sample injection.

In alternative embodiments, provided are methods comprising use of FISH, IHC or equivalent gene fusion detection protocols, and gene sequencing, wherein optionally the gene sequencing is high throughput or next generation gene sequencing, for the identification and characterization of gene abnormalities such as gene breakages; optionally gene breakages comprise gene translocation, gene rearrangements and/or gene inversions. In alternative embodiments, genes or transcripts are analyzed from individuals suspected of having cancer, and the analysis is carried out on biological samples taken from these individuals. This identification and characterization of gene abnormalities can be used in the diagnosis and treatment of a cancer.

In alternative embodiments, provided are methods comprising use of FISH, IHC or equivalent gene fusion detection protocols, and gene sequencing, wherein optionally the gene sequencing is high throughput or next generation gene sequencing, for the identification and characterization of gene abnormalities such as gene breakages; optionally gene breakages comprise gene translocation, gene rearrangements and/or gene inversions. In alternative embodiments, genes or transcripts are analyzed from individuals suspected of having cancer, and the analysis is carried out on biological samples taken from these individuals. This identification and characterization of gene abnormalities can be used in the diagnosis and treatment of a cancer.

Described herein, among other things, is a method of estimating efficiency of an oligonucleotide synthesis reaction. In some embodiments, the method comprises subjecting the products of one or more oligonucleotide synthesis reactions to LC-MS to produce a series of mass spectra, analyzing the mass spectra, and estimating the overall efficiency of an oligonucleotide synthesis reaction and/or the efficiency of addition of one or more of G, A, T or C individually in an oligonucleotide synthesis reaction.

Described herein, among other things, is a method of estimating efficiency of an oligonucleotide synthesis reaction. In some embodiments, the method comprises subjecting the products of one or more oligonucleotide synthesis reactions to LC-MS to produce a series of mass spectra, analyzing the mass spectra, and estimating the overall efficiency of an oligonucleotide synthesis reaction and/or the efficiency of addition of one or more of G, A, T or C individually in an oligonucleotide synthesis reaction.

Provided herein are methods, processes, systems, machines and apparatuses for non-invasive assessment of genetic variations.