Abstract: The disclosure provides methods and kits for the classification of biological samples into clinically relevant categories. The method comprises the steps of (i) determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop of at least 100,000 cfDNA fragments by alignment to a reference sequence, and (ii) determining in the reference sequence all nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides. Said nucleotides are: (a) within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or (b) within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i).

Abstract: The invention provides methods for assessment of risk for genetic conditions using target-enriched multiplexed parallel analysis, for example fetal risk for genetic conditions in prenatal testing. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods of the disclosure can be used to determine carrier status of inheritable genetic abnormalities associated with genetic conditions and from this information the fetal risk of inheriting the genetic condition can be determined. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for assessment of fetal DNA samples using target-enriched multiplexed parallel analysis. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods can be used with fetal or embryonic DNA samples, for example for the detection of the presence of genetic abnormalities, e.g., for purposes of IVF Pre-implantation Genetic Screening (PGS) and Diagnosis (PGD). Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for assessment of fetal DNA samples using target-enriched multiplexed parallel analysis. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods can be used with fetal or embryonic DNA samples, for example for the detection of the presence of genetic abnormalities, e.g., for purposes of IVF Pre-implantation Genetic Screening (PGS) and Diagnosis (PGD). Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for assessment of tumor biomarkers using target-enriched multiplexed parallel analysis. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods can be used with DNA samples from a patient, such as a tissue biopsy or plasma sample (liquid biopsy), for detection of the presence of tumor biomarkers, e.g., for purposes of diagnosis, screening, therapy selection and/or treatment monitoring. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for non-invasive prenatal testing that allow for detecting risk of chromosomal and subchromosomal abnormalities, including but not limited to aneuploidies, microdeletions and microduplications, insertions, translocations, inversions and small-size mutations including point mutations and mutational signatures. The methods of the invention utilize a pool of TArget Capture Sequences (TACS) to enrich for sequences of interest in a mixed sample containing both maternal and fetal DNA, followed by massive parallel sequencing and statistical analysis of the enriched population to thereby detect the risk of a genetic abnormality in the fetal DNA. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for non-invasive prenatal testing that allow for detecting risk of chromosomal and subchromosomal abnormalities, including but not limited to aneuploidies, microdeletions and microduplications, insertions, translocations, inversions and small-size mutations including point mutations and mutational signatures. The methods of the invention utilize a pool of TArget Capture Sequences (TACS) to enrich for sequences of interest in a mixed sample containing both maternal and fetal DNA, followed by massive parallel sequencing and statistical analysis of the enriched population to thereby detect the risk of a genetic abnormality in the fetal DNA. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for assessment of fetal DNA samples using target-enriched multiplexed parallel analysis. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods can be used with fetal or embryonic DNA samples, for example for the detection of the presence of genetic abnormalities, e.g., for purposes of IVF Pre-implantation Genetic Screening (PGS) and Diagnosis (PGD). Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for assessment of risk for genetic conditions using target-enriched multiplexed parallel analysis, for example fetal risk for genetic conditions in prenatal testing. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods of the disclosure can be used to determine carrier status of inheritable genetic abnormalities associated with genetic conditions and from this information the fetal risk of inheriting the genetic condition can be determined. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides methods for non-invasive prenatal testing that allow for detecting risk of chromosomal and subchromosomal abnormalities, including but not limited to aneuploidies, microdeletions and microduplications, insertions, translocations, inversions and small-size mutations including point mutations and mutational signatures. The methods of the invention utilize a pool of TArget Capture Sequences (TACS) to enrich for sequences of interest in a mixed sample containing both maternal and fetal DNA, followed by massive parallel sequencing and statistical analysis of the enriched population to thereby detect the risk of a genetic abnormality in the fetal DNA. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides improved methods for enriching targeted genomic regions of interest to be analyzed by multiplexed parallel sequencing. The methods of the invention utilize a pool of TArget Capture Sequences (TACS), wherein the pool comprises a plurality of TACS families, each member of a family binding to the same target sequence but with different start and/or stop positions on the sequence (i.e., staggered binding of the family members to the target sequence) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods of the invention can be used for a variety of clinical purposes, including non-invasive prenatal testing for chromosomal abnormalities, for example using a maternal blood sample or a sample of fetal cells, assessment of maternal and paternal carrier status for genetic disorders and detection of tumor biomarkers (e.g., liquid biopsy).

Abstract: The invention provides methods for non-invasive prenatal testing that allow for detecting risk of chromosomal and subchromosomal abnormalities, including but not limited to aneuploidies, microdeletions and microduplications, insertions, translocations, inversions and small-size mutations including point mutations and mutational signatures. The methods of the invention utilize a pool of TArget Capture Sequences (TACS) to enrich for sequences of interest in a mixed sample containing both maternal and fetal DNA, followed by massive parallel sequencing and statistical analysis of the enriched population to thereby detect the risk of a genetic abnormality in the fetal DNA. Kits for carrying out the methods of the invention are also provided.