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Nanopore RNA Sequencing Revealed Long Non-Coding and LTR Retrotransposon-Related RNAs Expressed at Early Stages of Triticale SEED Development is a 3rd generation NGS

The application can be compared to scFAST-seq and a fake long read 2nd genetation NGS

The Combinatin tumour researchon of Single cell Mutation Expression Analysis 


Projects like TCGA and ICGC had depicted mutation patterns in various cancer tissues, but the tumour

microenvironment remains unclear. Although the human tumour atlas network (HTAN), which utilizes 3'

single-cell transcriptome-seq technology, has provided valuable information on the cellular composition, it

cannot detect mutations, leaving many questions and assumptions in  tumour research, for example:


1. Do driver mutations really occur in just tumour cells?

2. If some mutations make cancer cells sensitive to certain treatments, why do some patients still have no response to those treatments?

3.

3. Tumours are the result of accumulated gene mutations. How many mutations do normal cells need to accumulate to become

tumour cells, and what functional impact do these mutations have on tumour cells?

4. When multiple mutations or co-mutations occur, are they in the same group of cancer cells or different ones, and how can we

distinguish when considering therapeutic methods for patients?

5. What is the underlying mechanism of tumour metastasis, which tumour clone contributes to the metastasis, what are their

characteristics, and how can we control it?

6. Is acquired resistance caused by new mutations or transcriptional reprogramming during therapy?

7.

7. In the era of precision medicine, how can we effectively select appropriate drug targets and tailor effective treatments based

on the specific characteristics of individual patients?

 

Tumours exhibit dual heterogeneity in mutation and expression, where mutations are the

"cause" and phenotype is the "effect". Detecting both mutations and expression within single

cells is essential for a comprehensive understanding of challenging questions. The innovative

scFAST-seq technology captures full-length RNAs with random primers to detect both

mutation and expression, providing novel insights for scientific research on tumour

development and metastasis.

1. Mutation-induced functional changes and indications for combination therapy


Figure 1.  Expression of CD47 in cells with KRAS       mutants and KRAS     .

Compared to KRAS   , CD47 is significantly upregulated in KRAS     , which

releases "Don't eat me" signals to macrophages and achieves immune

escape. This implies combined CD47-targeted drugs may lead to better

therapeutic effects.

 

Application:

Mutation-induced

Mutation-induced changes in cell expression and function, screening drug

target databases, exploring combination therapy targets, and achieving

personalized precisi

on treatment.

2. Locating co-mutations

3.Tracing mutated single cells

 

Figure 2. Differences in mutations between primary and metastatic tumours.

Metastatic tumour shows a higher number of tumour cells with KRAS and

TP53 co-mutations compared to primary tumour, suggesting that cells with

KRAS and TP53 co-mutations may have a high metastatic potential (yellow

dots represent a cell with both KRAS and TP53 mutations).

Application:

Investigate the impact of co-mutation on cell function and provide new

Investigate the impact of co-mutation on cell function and provide new

perspectives for cancer therapi

es.

l subpopulations

4. Research on the process 

Figure 3. A drug-related mutation at the Y position of gene X is specifically

present in "non-tumour cells".

A. Cell clusters and annotation;

B. Expression of gene X in different cell groups;

C. Coverage of the Y position of gene X in single cells: each dot represents a

cell,with red dots indicati

Application

umour occurrence and devel

ng detection of the Y position sequence of gene X

in the cell, and gray dots indicati

ng no coverage of the Y position of gene X in

the cell.

D. The Y position mutation of gene X is specifically present in non-epithelial

cells (the gene and site information is not shown because the data has not

been published).

Application: This gives us a hint that precision medicine guidance should

not solely rely on the detection of mutations, but also on the identification

of the cells carrying these mutations.

 


Figure 4. Mutation accumulation along the trajectory from normal

epitheli

al cells to tumour cells. Meanwhile, the trend of changes in gene

expression along the trajectory can be analyzed.

Applications-Describe the dynamic evolution process of mutation accumulation; search

for biomarkers related to early screening, diagnosis, and prognosis of

tumours.-Use PDX/organoid models to perform scFAST-seq detection before and

after drug treatment; explore drug sensitivity-related biomarkers; study

drug-resistant mutations or transcriptional reprogramming that occur

during the drug resistance progress.

Comparison

scFAST-seq, self-developed by Beijing SeekGene BioSciences Co., Ltd

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