Single cell analysis from tumor tissue comprising tumor cells and immune competent cells and from peripheral white blood cells are used to obtain an immunome signature, and to gain information about the TCR repertoire. Such information is then employed to generate recombinant and patient specific therapeutic cells, including T cells (including T effector memory, T memory stem, naïve T, T central memory, CD8+ T, and CD4+ T cells), NK cells (cord-blood derived or PBMC derived or NK92), NKT cells, and dendritic cells.

Disclosed herein include systems, methods, compositions, and kits for determining the expression of highly expressed proteins and lowly expressed proteins. In some embodiments, primers allowing generation of separate libraries for abundant AbSeq protein profiling oligonucleotides and scarce AbSeq protein profiling oligonucleotides are provided.

The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain comprising an alpha chain variable domain and a beta chain comprising a beta chain variable domain and the library comprises more than one TRAV gene product and/or more than one TRBV gene product, wherein the beta chain variable domain does not comprise one or more of a TRBV5-1, 5-3, 5-4, 5-5, 5-6, 5-7 or 5-8 gene product and wherein the plurality of TCRs do not consist essentially of TCRs comprising a TRAV12-2 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire and TCRs comprising a TRAV21 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire.

Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

Disclosed herein include systems, methods, compositions, and kits for determining the expression of highly expressed proteins and lowly expressed proteins. In some embodiments, primers allowing generation of separate libraries for abundant AbSeq protein profiling oligonucleotides and scarce AbSeq protein profiling oligonucleotides are provided.

The present invention relates to a method for the detection of genetic and or genomic abnormalities in a mixed sample, comprising the steps of biochemical and in-silico enrichment of a subset of cell-free DNA fragments derived from the mixed sample. The invention utilizes a pool of long DNA probes to enrich for sequences of interest in the mixed sample, followed by massive parallel sequencing and a computer-based analysis of the enriched sub-population to detect a risk of genetic and/or genomic abnormalities in the said sub-population of the mixed sample. The computer-based part of the method does not necessarily require alignment on a reference genome nor calibration values using reference samples. The method also comprises a kit for performing the invention.

The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein are methods of designing, making, and using the cancer assay panel for the diagnosis of cancer.

The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein are methods of designing, making, and using the cancer assay panel for the diagnosis of cancer.

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.