Table 1 Advantages and disadvantages of various research methods to measure heterogeneity
From: Breast cancer heterogeneity and its implication in personalized precision therapy
State of sample | Application | Example | Advantages | Disadvantages | Refs. |
|---|---|---|---|---|---|
Mixed cellular populations | At genomic and transcriptomic levels | Sanger sequencing | High accuracy | Laborious, expensive, lack of single-cell information and spatial information | [195] |
At the epigenomic level | NOMe–seq | Single-molecule real-time sequencing | Limited by the incompleteness of the human genome reference, with large gaps persisting in highly repetitive areas | [196] | |
At the proteomic level | Chromatography-based techniques, ELISA, western blotting, protein microarray, gel-based approaches | Identification of biomolecules using inherent properties, sequence of molecules, electrical charge | High effects of low quality and/or quantity of biomolecules. Limited in identification of rare peptides | ||
MS | Label-free. High throughput. Identification of posttranslational modifications | High complexity of analysis. Limited in identification of rare peptides | |||
Edman sequencing | Useful for the elucidation of residue deletions, the presence of common stable derivatives, and for following the progress of the synthesis itself | Limited in quantitation and the type and degree of adduct formation | |||
Single cells | At the genomic level | HM-SNS | Preserving single-cell information. High throughput | Loss of spatial information | |
Modular single CTC analysis pipeline | Each step is adjustable. Preserving single-cell information | Loss of spatial information | [60] | ||
At the epigenomic level | scATAC-seq | Preserving single-cell information | Loss of spatial information | [10] | |
scDNase-seq | Preserving single-cell information | Loss of spatial information | [11] | ||
scNOMe–seq | Preserving single-cell information | Loss of spatial information | [12] | ||
scChIP-seq | Preserving single-cell information. High throughput | Chip design is highly complex. Loss of spatial information | [202] | ||
At the transcriptomic level | scRNA-seq | Preserving single-cell information | Loss of spatial information | ||
At the proteomic level | OFCM | Preserving single-cell information. Counting in real time | Loss of spatial information. Chip design is highly complex | [210] | |
LC-Q-TOF-MS/MS | Preserving single-cell information | Loss of spatial information | |||
Tissue slices | At the genomic level | TSCS | Preserving single-cell information. Preserving spatial information | High complexity in use | [213] |
At the epigenomic level | SNuBar-ATAC | Preserving single-cell information. Preserving spatial information. Highly accurate. Easy to use. High throughput | Loss of partial sequencing reads. Mapping rate is not very high | [214] | |
At the transcriptomic level | FluoELs | Preserving single-cell information. Preserving spatial information. Error-correcting capability. Low cytotoxicity | Low throughput | [216] | |
CITE-seq | Preserving single-cell information. Preserving spatial information | Loss of information of some cell types | [19] | ||
At the proteomic level | MIBI-TOF | Preserving single-cell information. Preserving spatial information. Allow to revisit a sample after prolonged periods of time | Â | [217] | |
IMC | Preserving single-cell information. Preserving spatial information | Antibodies are not commercially available | |||
Organs/patients | Â | Mammography, US, and MRI | Relatively effective and widely adapted in hospitals | Excessive cost. Harmful radiation. Lacks sensibility. Inconvenience to the patients | [224] |
PET, SPECT | Effective in detection of metabolism and metastasis | Anatomical details are lacking | [225] | ||
Radiomics | Contain first-, second-, and higher-order statistics. Possibility of data sharing. Ability of quantitation | Difficulty in reproducibility | [228] |