This disclosure comprises devices and methods for determining the identity of individual protein molecules in a complex mixture.

A heuristic filtering system and method are described for variant DNA within a heterogeneous cell sample. After ion semiconductor sequencing, the amplicons are processed through a series of filters designed to eliminate noise in the variants to provide a clearer set of variant results. Reports are generated, showing both the filtered results and the effects the filters had on the original data.

The present invention relates to self-contained integrated systems and methods for constructing nucleic acid profiles of human individuals and for identification of the human individuals.

Systems and methods of providing run-time quality control and monitoring of a single or multiple sequencing runs are provided herein. In some embodiments, the run-time system includes or is in communication with a processor capable of determining various types of run-time information relating to the quality, progress, etc. of various sequencing runs. In some embodiments, the system can also be in communication with a user interface, for example, a GUI, capable of representing and communicating various types of information to a user regarding the quality of the individual or multiple runs, the functioning of the instrument, an error event, etc. Additionally, the system can capable of receiving actionable information from a user via the GUI thereby allowing the user to terminate or repeat various sequencing steps in a particular run, terminate a entire run, terminate all runs, allow a run to proceed, etc.

The present invention concerns methods for selecting and producing idiotype vaccines, and in particular methods for selecting and producing an idiotype vaccine for treatment of a B-cell derived malignancy in a subject based on the clonal profile (clonotype) of the malignancy; a method for producing an updated idiotype vaccine matched to a B-cell derived malignancy exhibiting a shifting clonal profile; and the high-fidelity idiotype vaccines produced using the methods. The invention also includes idiotype vaccines produced using the described methods and methods of treating B-cell derived malignancies using the produced vaccines.

A computer-implemented method for processing and/or analyzing nucleic acid sequencing data comprises receiving a first data input and a second data input. The first data input comprises untargeted sequencing data generated from a first nucleic acid sample obtained from a subject. The second data input comprises target-specific sequencing data generated from a second nucleic acid sample obtained from the subject. Next, with the aid of a computer processor, the first data input and the second data input are combined to produce a combined data set. Next, an output derived from the combined data set is generated. The output is indicative of the presence or absence of one or more polymorphisms of the first nucleic acid sample and/or the second nucleic acid sample.

Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.

Methods for selecting tag-oligonucleotide sequences for use in an in vitro nucleic acid assay. The selected tag sequences are useful for nucleic acid assay wherein interference between the nucleic acid sequences is the assay is to be controlled. Selected tag sequences are incorporated into nucleic acid assay to improve the performance of and/or minimize any interference between nucleic acids in the assay compared to untagged assays.

Systems, apparatus, and methods are provided for determining aberrations in a biological sample from an organism. Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Imbalances can be used to diagnose a patient for cancer, prognosticate a patient with cancer, or to detect the presence or monitor progress of a premalignant condition. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).

A sequence of polymer units in a polymer (3), eg. DNA, is estimated from at least one series of measurements related to the polymer, eg. ion current as a function of translocation through a nanopore (1), FIG. 6 wherein the value of each measurement is dependent on a k-mer being a group of k polymer units (4). A probabilistic model, especially a hidden Markov model (HMM), is provided, comprising, for a set of possible k-mers: transition weightings representing the chances of transitions from origin k-mers to destination k-mers; and emission weightings in respect of each k-mer that represent the chances of observing given values of measurements for that k-mer. The series of measurements is analysed using an analytical technique, eg. Viterbi decoding, that refers to the model and estimates at least one estimated sequence of polymer units in the polymer based on the likelihood predicted by the model of the series of measurements being produced by sequences of polymer units. In a further embodiment, different voltages are applied across the nanopore during translocation in order to improve the resolution of polymer units.