Abstract: The present disclosure provides methods and systems for systematic elimination of background DNA in a DNA mixture sample. Often, the DNA of interest is in a heavy background of DNAs from other tissues. For example, a majority of DNA in plasma cell-free DNA originates from white blood cells. The present disclosure exploits genome-wide background DNA methylation to systematically eliminate DNA from white blood cells and normal tissue(s), therefore enriching non-background DNA for diagnostics, for example, the diagnostics of cancer and infectious diseases. The methods and systems may comprise the selection of targeted regions to generate one or more hybrid capture panels, digest nucleic acid molecules of specific methylation status with one or more restriction enzymes, retrieve the remaining DNA using the hybrid capture panel, sequence the captured DNA, analyze the sequencing data of the captured DNA, and diagnose diseases.

Abstract: Disclosed herein are methods and systems of utilizing sequencing reads for detecting and quantifying the presence of a tissue type or a disease type in cell-free DNA prepared from blood samples.

Abstract: Disclosed herein are methods and systems of utilizing sequencing reads for detecting and quantifying the presence of a tissue type or a disease type in cell-free DNA prepared from blood samples.

Abstract: The present disclosure provides methods and compositions for preparation of a nucleic acid library. In some embodiments, the nucleic acids comprise cell-free DNA, including cfDNA that is in need of analysis, such as by sequencing. The methods may comprise restriction enzyme digestion, adapter ligation, and subsequent amplification, and may provide improved approaches for reducing the number adapter dimers produced during the process. In an aspect, a method for preparing a library of nucleic acids may comprise: digesting DNA molecules with restriction enzymes to produce DNA fragments; ligating adapters to the DNA fragments by incubating with ligase to produce a mixture of adapter-ligated DNA fragments and adapter dimers; amplifying the adapter-ligated DNA fragments to produce amplified adapter-ligated DNA fragments; and reducing the quantity of the adapter dimers by differentiating between the junction between an adapter and a DNA fragment, and the junction between an adapter and another adapter.

Abstract: The present disclosure provides methods and systems for detecting or inferring levels of Copy Number Variants (CNVs) in cell-free nucleic acid samples to detect or assess cancer and prenatal diseases. Cell-free nucleic acid methylation sequencing data may be utilized to distinguish tumor-derived or fetal-derived sequencing reads from normal cfDNA sequencing reads. Each cell-free nucleic acid sequencing read (e.g., containing tumor or fetal methylation markers) may be classified as corresponding to a tumor/fetal-derived or a normal-plasma cell-free nucleic acid, based on the methylation cfDNA sequencing data (e.g., obtained using Bisulfite sequencing or bisulfite-free sequencing methods) and tumor/fetal methylation markers. Next, a profile of the tumor/fetal-derived sequencing read counts may be constructed and then normalized. The CNV status (e.g., gain or loss) of each genomic region may be inferred, and a diagnosis or prognosis can be made based on a subjects inferred CNV profile.

Abstract: The present disclosure provides a probabilistic model for accurate and sensitive somatic single nucleotide variant (SNV) detection in cell-free nucleic acid samples comprising a set of sequence data. A joint genotype may be determined for each locus in the set of sequence data, and germline mutations may be intrinsically removed. A set of filtrations can be applied to eliminate low quality somatic variant calls. Further, a global tumor cell-free deoxyribonucleic acid (cfDNA) fraction and overlapping read mates can be considered, thereby enabling accurate SNV detection and variant allele frequency estimation from samples with low tumor cfDNA fraction. A sensitive early detection of minimal residual disease (MRD) is designed by using the probabilistic model and the machine learning model for distinguishing true variants from sequencing errors.

Abstract: Disclosed herein are methods and systems of utilizing sequencing reads for detecting and quantifying the presence of a tissue type or a disease type in cell-free DNA prepared from blood samples.

Abstract: A transformable garment that folds and envelops the wearer with a garment body with panels that use origami folding and shape memory alloy (SMA) elements to assist to transform the garment from an expanded state to a retracted state is provided. Garment designs with transformable panels and sleeves can benefit those who have trouble dressing by allowing the garment to wrap around and fit the wearer without outside help. These types of clothes are expected to be beneficial for people with Cerebral Palsy (CP) and also for populations with other body movement disorders and elderly people.