Positional Delivery and Encoding by Oligonucleotides of Biological Cells for Single Cell Sequencing (POS SEQ)

Abstract

Techniques for positional delivery and position encoding by oligonucleotides of biological cells for single cell RNA sequencing are provided. In one aspect, a method of positional delivery and encoding of cells in a biological sample includes: encoding the cells in the biological sample for single cell sequencing by delivering molecular probes inside the cells that encode a position of the cells in the biological sample. A system for positional delivery and encoding of cells in a biological sample is also provided.

What is claimed is: 
     
         1 . A system, comprising:
 a processor device, connected to a memory, that is implemented to:
 analyze data obtained by single cell sequencing of cells along with molecular probes, that have been delivered inside the cells, which uniquely encode a position of the cells in a biological sample. 
   
     
     
         2 . The system of  claim 1 , wherein the cells have been disassociated from the biological sample for the single cell sequencing. 
     
     
         3 . The system of  claim 2 , wherein the molecular probes encode positional data comprising the position of the cells in the biological sample, and wherein the molecular probes retain the positional data of the cells that have been disassociated from the biological sample. 
     
     
         4 . The system of  claim 1 , wherein the molecular probes comprise an oligonucleotide sequence that uniquely encodes the position of the cells in the biological sample. 
     
     
         5 . The system of  claim 4 , wherein the molecular probes further comprise:
 a polymerase chain reaction (PCR) handle;   a cell barcode; and   a unique molecular identifier (UMI).   
     
     
         6 . The system of  claim 5 , wherein the processor device is further implemented to:
 identify individual ones of the cells by the cell barcode.   
     
     
         7 . The system of  claim 5 , wherein the processor device is further implemented to:
 identify an original position of the cells within the biological sample via the oligonucleotide sequence.   
     
     
         8 . The system of  claim 5 , wherein the processor device is further implemented to:
 collect transcriptome information of the cells.   
     
     
         9 . The system of  claim 1 , wherein the biological sample is selected from the group consisting of: a cell culture, a tissue sample, and combinations thereof. 
     
     
         10 . The system of  claim 1 , wherein the single cell sequencing of the cells is performed using a technique selected from the group consisting of: drop-seq, seq-well, cyto-seq, and combinations thereof. 
     
     
         11 . A system, comprising:
 a processor device, connected to a memory, that is implemented to:
 analyze data obtained by single cell sequencing of cells along with molecular probes, that have been delivered inside the cells, which uniquely encode a position of the cells in a biological sample; and 
 collect from the data concomitant spatial and molecular measurements of one or more of the cells in the biological sample. 
   
     
     
         12 . The system of  claim 11 , wherein the cells have been disassociated from the biological sample for the single cell sequencing. 
     
     
         13 . The system of  claim 12 , wherein the molecular probes encode positional data comprising the position of the cells in the biological sample, and wherein the molecular probes retain the positional data of the cells that have been disassociated from the biological sample. 
     
     
         14 . The system of  claim 11 , wherein the molecular probes comprise an oligonucleotide sequence that uniquely encodes the position of the cells in the biological sample. 
     
     
         15 . The system of  claim 14 , wherein the molecular probes further comprise:
 a polymerase chain reaction (PCR) handle;   a cell barcode; and   a unique molecular identifier (UMI).   
     
     
         16 . The system of  claim 15 , wherein the processor device is further implemented to:
 identify individual ones of the cells by the cell barcode.   
     
     
         17 . The system of  claim 15 , wherein the processor device is further implemented to:
 identify an original position of the cells within the biological sample via the oligonucleotide sequence.   
     
     
         18 . The system of  claim 11 , wherein the molecular measurements comprise transcriptome information of the cells. 
     
     
         19 . The system of  claim 11 , wherein the biological sample is selected from the group consisting of: a cell culture, a tissue sample, and combinations thereof. 
     
     
         20 . The system of  claim 11 , wherein the single cell sequencing of the cells is performed using a technique selected from the group consisting of: drop-seq, seq-well, cyto-seq, and combinations thereof.