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Hierarchical clustering divided the progeny cell lines into two different taxonomic groups, of either adherent (293T, 293E) or suspension cell lines (293-H, 293-F and Freestyle 293-F), diverged from the parental HEK293.
|
[
{
"end": 116,
"label": "CellLine",
"start": 112,
"text": "293T"
},
{
"end": 122,
"label": "CellLine",
"start": 118,
"text": "293E"
},
{
"end": 155,
"label": "CellLine",
"start": 150,
"text": "293-H"
},
{
"end": 162,
"label": "CellLine",
"start": 157,
"text": "293-F"
},
{
"end": 176,
"label": "CellLine",
"start": 167,
"text": "Freestyle"
},
{
"end": 182,
"label": "CellLine",
"start": 177,
"text": "293-F"
},
{
"end": 218,
"label": "CellLine",
"start": 212,
"text": "HEK293"
}
] |
ChemBL_V1
|
Interestingly, the original HEK293 cell line was the most distant from all other cell lines.
|
[
{
"end": 34,
"label": "CellLine",
"start": 28,
"text": "HEK293"
}
] |
ChemBL_V1
|
As expected, the two 293-F lineages (293-F and Freestyle 293-F) showed very similar profiles.
|
[] |
ChemBL_V1
|
The same pattern of gene expression clustering was visualized by principal component analysis (Fig. 1d), where the suspension cell-lines grouped together in the plot, with a very close clustering of 293-F and Freestyle 293-F cells.
|
[
{
"end": 204,
"label": "CellLine",
"start": 199,
"text": "293-F"
},
{
"end": 224,
"label": "CellLine",
"start": 219,
"text": "293-F"
}
] |
ChemBL_V1
|
On the other hand, the adherent cell-lines 293E and 293T showed larger variations in gene expression patterns between cell lines.
|
[
{
"end": 47,
"label": "CellLine",
"start": 43,
"text": "293E"
},
{
"end": 56,
"label": "CellLine",
"start": 52,
"text": "293T"
}
] |
ChemBL_V1
|
The parental cell line HEK293 showed a notable difference in transcriptome profile compared to all the other cell lines along the first principal component (PC1).
|
[
{
"end": 29,
"label": "CellLine",
"start": 23,
"text": "HEK293"
}
] |
ChemBL_V1
|
These results indicate a genomic divergence of the clonal lineages compared to the parental HEK293 and suggest the presence of similar transcriptomic traits between HEK293 progeny cell lines individually selected for during the isolation of each clone.
|
[
{
"end": 98,
"label": "CellLine",
"start": 92,
"text": "HEK293"
},
{
"end": 171,
"label": "CellLine",
"start": 165,
"text": "HEK293"
}
] |
ChemBL_V1
|
Hierarchical clustering of the cell lines based on SNVs gave a slightly different trend compared to the transcriptomic comparison.
|
[] |
ChemBL_V1
|
A different pattern of overall clustering was observed, with the original HEK293 and 293E cell lines separated from the rest on a separate branch and the three suspension cell lines grouped on a second branch together with 293T.
|
[
{
"end": 80,
"label": "CellLine",
"start": 74,
"text": "HEK293"
},
{
"end": 89,
"label": "CellLine",
"start": 85,
"text": "293E"
},
{
"end": 227,
"label": "CellLine",
"start": 223,
"text": "293T"
}
] |
ChemBL_V1
|
However, 293-F and Freestyle 293-F were, as expected, the most similar cell lines also in this comparison (Supplementary Fig. S1).
|
[] |
ChemBL_V1
|
The overall number of genomic variations was similar between the cell lines and variations located to similar genomic regions (Supplementary Fig. S1).
|
[] |
ChemBL_V1
|
Moreover, the ratio between missense and synonomous SNVs in all cell lines ranged between 0.866 and 0.879, where the original HEK293 strain had the lowest ratio (Supplementary Fig. S1).
|
[
{
"end": 132,
"label": "CellLine",
"start": 126,
"text": "HEK293"
}
] |
ChemBL_V1
|
Pairwise comparisons of SNVs and indels between HEK293 and each progeny cell line showed that the highest number of high (variants expected to have a disruptive impact on the protein, for example protein truncation or loss of start/stop codon) and moderate (non-disruptive variant that might change protein effectiveness, for example a missense variant) SNVs and indels were seen for the two adherent cell lines 293E and 293T (Supplementary Fig. S1).
|
[
{
"end": 54,
"label": "CellLine",
"start": 48,
"text": "HEK293"
},
{
"end": 416,
"label": "CellLine",
"start": 412,
"text": "293E"
},
{
"end": 425,
"label": "CellLine",
"start": 421,
"text": "293T"
}
] |
ChemBL_V1
|
Genes with high impact SNVs in progeny cell lines compared to the parental HEK293 can be found in Supplementary Table S2.
|
[] |
ChemBL_V1
|
Amongst these, five genes had acquired high impact SNVs (PPP2R4, C9orf43, CTB-47B11.3, CYFIP2 and SGCD) in all progeny cell lines compared to the parental strain.
|
[] |
ChemBL_V1
|
Figure 1Comparisons of genomic and transcriptomic profiles of HEK293 cells showed taxonomic divergence between parental HEK293 and progeny cell lines. (
|
[
{
"end": 68,
"label": "CellLine",
"start": 62,
"text": "HEK293"
},
{
"end": 126,
"label": "CellLine",
"start": 120,
"text": "HEK293"
}
] |
ChemBL_V1
|
A schematic overview of the lineage relationship of the six HEK293 cell lines used in this study.
|
[
{
"end": 66,
"label": "CellLine",
"start": 60,
"text": "HEK293"
}
] |
ChemBL_V1
|
Blue dots represent adherent cells whereas grey dots represent suspension cell lines. (
|
[] |
ChemBL_V1
|
Genomic comparison between HEK293 cell lines based on Spearman correlation coefficients of read counts.
|
[
{
"end": 33,
"label": "CellLine",
"start": 27,
"text": "HEK293"
}
] |
ChemBL_V1
|
Darker blue color indicates higher correlation. (
|
[] |
ChemBL_V1
|
Sample-to-sample comparison between transcriptomes illustrated by a heatmap and hierarchical clustering of taxonomical divergence between samples.
|
[] |
ChemBL_V1
|
Darker blue color indicates shorter Euclidean distance between samples and more similarity. (
|
[] |
ChemBL_V1
|
PCA plot showing the separation in expression pattern between samples. (
|
[] |
ChemBL_V1
|
RNA expression levels (in DESeq2 median of ratios) and standard deviations (n = 3) of stably integrated viral genes (EBNA-1, Large T, E1A and E1B) in HEK293 cell lineages determined by RNA sequencing.
|
[
{
"end": 156,
"label": "CellLine",
"start": 150,
"text": "HEK293"
}
] |
ChemBL_V1
|
Comparisons of genomic and transcriptomic profiles of HEK293 cells showed taxonomic divergence between parental HEK293 and progeny cell lines. (
|
[
{
"end": 60,
"label": "CellLine",
"start": 54,
"text": "HEK293"
},
{
"end": 118,
"label": "CellLine",
"start": 112,
"text": "HEK293"
}
] |
ChemBL_V1
|
A schematic overview of the lineage relationship of the six HEK293 cell lines used in this study.
|
[
{
"end": 66,
"label": "CellLine",
"start": 60,
"text": "HEK293"
}
] |
ChemBL_V1
|
Blue dots represent adherent cells whereas grey dots represent suspension cell lines. (
|
[] |
ChemBL_V1
|
Genomic comparison between HEK293 cell lines based on Spearman correlation coefficients of read counts.
|
[
{
"end": 33,
"label": "CellLine",
"start": 27,
"text": "HEK293"
}
] |
ChemBL_V1
|
Darker blue color indicates higher correlation. (
|
[] |
ChemBL_V1
|
Sample-to-sample comparison between transcriptomes illustrated by a heatmap and hierarchical clustering of taxonomical divergence between samples.
|
[] |
ChemBL_V1
|
Darker blue color indicates shorter Euclidean distance between samples and more similarity. (
|
[] |
ChemBL_V1
|
PCA plot showing the separation in expression pattern between samples. (
|
[] |
ChemBL_V1
|
RNA expression levels (in DESeq2 median of ratios) and standard deviations (n = 3) of stably integrated viral genes (EBNA-1, Large T, E1A and E1B) in HEK293 cell lineages determined by RNA sequencing.
|
[
{
"end": 156,
"label": "CellLine",
"start": 150,
"text": "HEK293"
}
] |
ChemBL_V1
|
The HEK293 cell line was originally immortalized by the random integration of viral genomic DNA of adenovirus 5, which includes the E1A and E1B genes.
|
[
{
"end": 10,
"label": "CellLine",
"start": 4,
"text": "HEK293"
}
] |
ChemBL_V1
|
In this study, overall high mRNA levels of E1A and E1B were observed in all HEK293 cell lines (Supplementary Fig. S2).
|
[
{
"end": 82,
"label": "CellLine",
"start": 76,
"text": "HEK293"
}
] |
ChemBL_V1
|
A comparison of mRNA levels of the viral element E1A showed significantly (p < 0.05) higher expression in HEK293 compared to both 293T and Freestyle 293-F. In addition, both 293E and 293-H had significantly higher expression than 293T, 293-F and Freestyle 293-F. Further, 293-F had significantly higher expression than Freestyle 293-F. (Supplementary Fig. S1) The analysis of the viral element E1B showed that 293-F had significantly higher expression (p < 0.05) than 293-H and Freestyle 293-F (Supplementary Fig. S1).
|
[
{
"end": 112,
"label": "CellLine",
"start": 106,
"text": "HEK293"
},
{
"end": 134,
"label": "CellLine",
"start": 130,
"text": "293T"
},
{
"end": 178,
"label": "CellLine",
"start": 174,
"text": "293E"
},
{
"end": 234,
"label": "CellLine",
"start": 230,
"text": "293T"
},
{
"end": 241,
"label": "CellLine",
"start": 236,
"text": "293-F"
}
] |
ChemBL_V1
|
As expected, the gene expression of Large T and EBNA-1 was detected in 293T and 293E, respectively (Fig. 1e).
|
[
{
"end": 75,
"label": "CellLine",
"start": 71,
"text": "293T"
},
{
"end": 84,
"label": "CellLine",
"start": 80,
"text": "293E"
}
] |
ChemBL_V1
|
Interestingly, expression of the Large T antigen was also observed in 293E, which is not reported by the supplier (ATCC).
|
[
{
"end": 74,
"label": "CellLine",
"start": 70,
"text": "293E"
}
] |
ChemBL_V1
|
The presence of a truncated version of Large T in the 293E genome was confirmed by de novo assembly of all reads not mapping to the human reference genome (Supplementary Fig. S2).
|
[] |
ChemBL_V1
|
Tracing the origin of the 293E cell line, the Large T expression of 293E may be derived from the pRSVneo plasmid that was used to co-transfect HEK293 cells along with the pCMV-EBNA plasmid for the generation of the stable EBNA-1 expressing clone (293c18) by geneticin (G418) selection.
|
[
{
"end": 30,
"label": "CellLine",
"start": 26,
"text": "293E"
},
{
"end": 149,
"label": "CellLine",
"start": 143,
"text": "HEK293"
},
{
"end": 253,
"label": "CellLine",
"start": 247,
"text": "293c18"
}
] |
ChemBL_V1
|
The pRSVneo plasmid contains a truncated version of the Large T gene (according to the AddGene vector Database), which aligns perfectly with the truncated Large T sequence found in the 293E genome (Supplementary Fig. S2).
|
[] |
ChemBL_V1
|
In order to evaluate the genomic variation between HEK293 and its derivatives further, overall genomic copy number variation of all progeny cell lines compared to the parental HEK293 was performed.
|
[
{
"end": 57,
"label": "CellLine",
"start": 51,
"text": "HEK293"
},
{
"end": 182,
"label": "CellLine",
"start": 176,
"text": "HEK293"
}
] |
ChemBL_V1
|
A comparison of gained and lost regions on all chromosomes between all cell lines can be found in Supplementary Fig. S3 and Table S3.
|
[] |
ChemBL_V1
|
Interestingly, a conserved pattern of copy number gain or loss of large regions has occurred on several chromosomes of all HEK293 progeny cells compared to HEK293, whereas other changes are more local or cell line specific.
|
[
{
"end": 129,
"label": "CellLine",
"start": 123,
"text": "HEK293"
},
{
"end": 162,
"label": "CellLine",
"start": 156,
"text": "HEK293"
}
] |
ChemBL_V1
|
For instance, on chromosome 13, a region of > 15 Mb has been amplified in all cell lines compared to the parental HEK293 strain (Fig. 2a).
|
[
{
"end": 120,
"label": "CellLine",
"start": 114,
"text": "HEK293"
}
] |
ChemBL_V1
|
All elements with copy number gain of > 1 log2 fold-change common to all progenitor cells are located in this region (Supplementary Table S3).
|
[] |
ChemBL_V1
|
Amongst these, four out of seven protein-coding genes (BORA, MZT1, PIBF1 and KLHL1) belong to the cytoskeleton gene set (GO: 0005856).
|
[] |
ChemBL_V1
|
On chromosome 18, there is a conserved pattern of copy number loss of most of the chromosome sequence for all progeny cell lines compared to the parental HEK293 strain, with the exception of a high degree of copy number gain (> 0.8 log2 fold-change) of a region close to the centromere for all cell lines except 293E (Fig. 2a).
|
[
{
"end": 160,
"label": "CellLine",
"start": 154,
"text": "HEK293"
},
{
"end": 316,
"label": "CellLine",
"start": 312,
"text": "293E"
}
] |
ChemBL_V1
|
Within the region of conserved gain are several genes encoding cell adhesion molecules within the desmocollin (DSC) and desmoglein (DSG) subfamilies, belonging to the cell–cell adhesion gene set (GO: 0098609).
|
[] |
ChemBL_V1
|
When analyzing more local copy number variations between progeny cell lines and the parental strain, some interesting loss or gain of full or partial elements compared to the parental HEK293 were identified.
|
[
{
"end": 190,
"label": "CellLine",
"start": 184,
"text": "HEK293"
}
] |
ChemBL_V1
|
For instance, copy number loss was observed for the fumarate hydratase (FH) gene, which has previously been reported to have lost several gene copies in HEK293 and hence been hypothesized to play a role in the phenotypic transformation of HEK293.
|
[
{
"end": 159,
"label": "CellLine",
"start": 153,
"text": "HEK293"
},
{
"end": 245,
"label": "CellLine",
"start": 239,
"text": "HEK293"
}
] |
ChemBL_V1
|
Interestingly, the fumarate hydratase gene along with the neighboring kynurenine 3-monooxygenase (KMO) gene, had a log2-fold copy ratio of < -1 in 293E, 293-F and Freestyle 293-F cell lines compared to the parental HEK293 (Fig. 2b and Supplementary Fig. S4), suggesting that these cells have half the number of copies compared to the parental cell line.
|
[
{
"end": 151,
"label": "CellLine",
"start": 147,
"text": "293E"
},
{
"end": 158,
"label": "CellLine",
"start": 153,
"text": "293-F"
},
{
"end": 178,
"label": "CellLine",
"start": 173,
"text": "293-F"
},
{
"end": 221,
"label": "CellLine",
"start": 215,
"text": "HEK293"
}
] |
ChemBL_V1
|
Moreover, the 293T and 293-H cell lines have a gain of the genomic loci surrounding the FH gene, while maintaining the copy number of the FH gene compared to HEK293.
|
[
{
"end": 18,
"label": "CellLine",
"start": 14,
"text": "293T"
},
{
"end": 28,
"label": "CellLine",
"start": 23,
"text": "293-H"
},
{
"end": 164,
"label": "CellLine",
"start": 158,
"text": "HEK293"
}
] |
ChemBL_V1
|
Interestingly, the resulting FH expression levels of the cell lines only partly reflected the gene copy number changes (Fig. 2b and Supplementary Fig. S4).
|
[] |
ChemBL_V1
|
Even though the gene copy number of the parental HEK293 strain is the same as for 293T and 293-H lineages, the FH mRNA levels of HEK293 was as low as the expression levels of the lineages with only half the number of FH gene copies.
|
[
{
"end": 55,
"label": "CellLine",
"start": 49,
"text": "HEK293"
},
{
"end": 86,
"label": "CellLine",
"start": 82,
"text": "293T"
},
{
"end": 96,
"label": "CellLine",
"start": 91,
"text": "293-H"
},
{
"end": 135,
"label": "CellLine",
"start": 129,
"text": "HEK293"
}
] |
ChemBL_V1
|
Moreover, the expression levels of KMO was comparably low in all cell lines but did not correlate with gene copy number.
|
[] |
ChemBL_V1
|
Besides the changes in gene copy number of the FH locus, a locus around the transducin-like enhancer protein 4 (TLE4) gene, encoding a transcriptional co-repressor of Wnt signaling pathway members was found to have a log2-fold copy number gain of > 1.5 in all progeny cell lines except for 293E (Fig. 2b).
|
[] |
ChemBL_V1
|
This gain in the TLE4 locus was accordingly reflected in the transcription level of the gene with a higher level of expression in 293T, 293-H, 293-F and Freestyle 293-F compared to 293E and HEK293 (Supplementary Fig. S4).
|
[
{
"end": 134,
"label": "CellLine",
"start": 130,
"text": "293T"
},
{
"end": 141,
"label": "CellLine",
"start": 136,
"text": "293-H"
},
{
"end": 148,
"label": "CellLine",
"start": 143,
"text": "293-F"
},
{
"end": 162,
"label": "CellLine",
"start": 153,
"text": "Freestyle"
},
{
"end": 168,
"label": "CellLine",
"start": 163,
"text": "293-F"
},
{
"end": 185,
"label": "CellLine",
"start": 181,
"text": "293E"
},
{
"end": 196,
"label": "CellLine",
"start": 190,
"text": "HEK293"
}
] |
ChemBL_V1
|
In addition, a major loss of copy number of the ADAM3A pseudogene was observed for all cell lines except 293-H with a maintained low or no expression of the pseudogene observed in the cell lines (Fig. 2a,b and Supplementary Fig. S4).Figure 2Copy number variation analysis of HEK293 progeny cells compared to the parental HEK293 revealed conserved patterns of copy number gain and loss. (
|
[
{
"end": 110,
"label": "CellLine",
"start": 105,
"text": "293-H"
},
{
"end": 281,
"label": "CellLine",
"start": 275,
"text": "HEK293"
},
{
"end": 327,
"label": "CellLine",
"start": 321,
"text": "HEK293"
}
] |
ChemBL_V1
|
Genomic copy number gain (red) or loss (blue) of chromosomes 1, 8, 9, 13 and 18 of progeny HEK293 cell lines compared to parental HEK293 cells.
|
[
{
"end": 97,
"label": "CellLine",
"start": 91,
"text": "HEK293"
},
{
"end": 136,
"label": "CellLine",
"start": 130,
"text": "HEK293"
}
] |
ChemBL_V1
|
The black line indicates the centromere position of each chromosome. (
|
[] |
ChemBL_V1
|
Genomic copy number gain or loss (log2 fold change) compared to HEK293 for each cell line of the FH, KMO, TLE4 and ADAM3A genes.
|
[
{
"end": 70,
"label": "CellLine",
"start": 64,
"text": "HEK293"
},
{
"end": 104,
"label": "CellLine",
"start": 101,
"text": "KMO"
}
] |
ChemBL_V1
|
Copy number variation analysis of HEK293 progeny cells compared to the parental HEK293 revealed conserved patterns of copy number gain and loss. (
|
[
{
"end": 40,
"label": "CellLine",
"start": 34,
"text": "HEK293"
},
{
"end": 86,
"label": "CellLine",
"start": 80,
"text": "HEK293"
}
] |
ChemBL_V1
|
Genomic copy number gain (red) or loss (blue) of chromosomes 1, 8, 9, 13 and 18 of progeny HEK293 cell lines compared to parental HEK293 cells.
|
[
{
"end": 97,
"label": "CellLine",
"start": 91,
"text": "HEK293"
},
{
"end": 136,
"label": "CellLine",
"start": 130,
"text": "HEK293"
}
] |
ChemBL_V1
|
The black line indicates the centromere position of each chromosome. (
|
[] |
ChemBL_V1
|
Genomic copy number gain or loss (log2 fold change) compared to HEK293 for each cell line of the FH, KMO, TLE4 and ADAM3A genes.
|
[
{
"end": 70,
"label": "CellLine",
"start": 64,
"text": "HEK293"
},
{
"end": 104,
"label": "CellLine",
"start": 101,
"text": "KMO"
}
] |
ChemBL_V1
|
Due to the observed pattern of common genomic changes to progeny cell lines compared to the parental HEK293, an evaluation of common SNPs amongst all progeny cell lines but not HEK293 was performed.
|
[
{
"end": 107,
"label": "CellLine",
"start": 101,
"text": "HEK293"
},
{
"end": 183,
"label": "CellLine",
"start": 177,
"text": "HEK293"
}
] |
ChemBL_V1
|
GO enrichment analysis of common genes with high or moderate impact SNPs different in all progeny cell lines compared to the original HEK293 (Supplementary Table S4), showed significant (adjusted p-value < 0.05) enrichment of homophilic cell adhesion via plasma membrane adhesion molecules (GO:0007156; adjusted p-value 0.025; fold enrichment 10.26; data not shown) and cell–cell adhesion via plasma-membrane adhesion molecules (GO:0098742; adjusted p-value 0.032; fold enrichment 7.53; data not shown).
|
[
{
"end": 140,
"label": "CellLine",
"start": 134,
"text": "HEK293"
}
] |
ChemBL_V1
|
All genes with moderate or high impact SNPs in progeny cell lines compared to HEK293 found amongst both these GO-terms were protocadherins (PCDH12, PCDHB10, PCDHB13, PCDHB15, PCDHB16 PCDHGA2, PCDHGA3 and PCDHGB2).
|
[] |
ChemBL_V1
|
In addition, the Teneurin-2 gene (TENM2) (within GO:0098742) had an altered SNP allele in all progeny cell lines compared to HEK293.
|
[
{
"end": 131,
"label": "CellLine",
"start": 125,
"text": "HEK293"
}
] |
ChemBL_V1
|
These SNPs all result in missense mutations with unknown biological impact on the gene products.
|
[] |
ChemBL_V1
|
However, the enrichment of common SNPs within this group of genes in all HEK293 progeny cell lines may suggest an impact on the protein function and a selective advantage of such phenotypic changes during continuous cell line cultivation.
|
[
{
"end": 79,
"label": "CellLine",
"start": 73,
"text": "HEK293"
}
] |
ChemBL_V1
|
Based on the overall genomic and transcriptomic profiles of the different HEK293 cell lines, the parental HEK293 strain stood out as different compared to all other cell lines.
|
[
{
"end": 80,
"label": "CellLine",
"start": 74,
"text": "HEK293"
},
{
"end": 112,
"label": "CellLine",
"start": 106,
"text": "HEK293"
}
] |
ChemBL_V1
|
In order to evaluate common changes between all progeny cell lines and the parental HEK293, differential expression analysis was performed.
|
[
{
"end": 90,
"label": "CellLine",
"start": 84,
"text": "HEK293"
}
] |
ChemBL_V1
|
Results showed a significant consensus of down-regulation of genes involved in extracellular matrix organization, locomotion and cell adhesion in progeny cells compared to the parental HEK293 strain (Fig. 3a).
|
[
{
"end": 191,
"label": "CellLine",
"start": 185,
"text": "HEK293"
}
] |
ChemBL_V1
|
Moreover, amino acid metabolism and metabolic process of small molecules were found up-regulated in all progeny cell-lines.
|
[] |
ChemBL_V1
|
Along with changes in extracellular matrix genes, there is also a consensus amongst progeny cell lines compared to HEK293 of differential expression of genes involved in other types of cellular component organization such as cell morphogenesis, cytoskeleton-, membrane- and cell junction organization.
|
[
{
"end": 121,
"label": "CellLine",
"start": 115,
"text": "HEK293"
}
] |
ChemBL_V1
|
A comparison between gene expression fold changes and copy number variation of the differentially expressed genes (log2-fold change > ± 1) for each progeny cell line compared to HEK293 showed a trend of gained gene copies amongst the majority of genes with up-regulated mRNA levels (Supplementary Fig. S4).
|
[
{
"end": 184,
"label": "CellLine",
"start": 178,
"text": "HEK293"
}
] |
ChemBL_V1
|
However, there was not a clear trend of loss in gene copy number amongst transcriptionally down-regulated genes for any cell line.
|
[] |
ChemBL_V1
|
Figure 3Differential expression analysis emphasized processes and genes with common changes in all progeny cell lines compared to the parental HEK293. (
|
[
{
"end": 149,
"label": "CellLine",
"start": 143,
"text": "HEK293"
}
] |
ChemBL_V1
|
Consensus heatmap of GO biological processes with a different expression pattern between progeny cell lines compared to the parental HEK293.
|
[
{
"end": 139,
"label": "CellLine",
"start": 133,
"text": "HEK293"
}
] |
ChemBL_V1
|
Low consensus scores, represented by a dark blue color, indicate more significant differences. (
|
[] |
ChemBL_V1
|
Common differentially expressed (DE) genes in pairwise comparisons of all HEK293 cells.
|
[] |
ChemBL_V1
|
Blue bars show number of DE genes in each pairwise comparison.
|
[] |
ChemBL_V1
|
Green bar shows 329 common DE genes in pairwise comparisons of progeny with HEK293 parental cells.
|
[] |
ChemBL_V1
|
Red bar shows common 38 DE genes in the comparison of suspension cells against adherent cells. (
|
[] |
ChemBL_V1
|
Top ten significant GO cellular components of the 329 common DE genes in pairwise comparisons between progeny cells and HEK293.
|
[
{
"end": 126,
"label": "CellLine",
"start": 120,
"text": "HEK293"
}
] |
ChemBL_V1
|
Differential expression analysis emphasized processes and genes with common changes in all progeny cell lines compared to the parental HEK293. (
|
[
{
"end": 141,
"label": "CellLine",
"start": 135,
"text": "HEK293"
}
] |
ChemBL_V1
|
Consensus heatmap of GO biological processes with a different expression pattern between progeny cell lines compared to the parental HEK293.
|
[
{
"end": 139,
"label": "CellLine",
"start": 133,
"text": "HEK293"
}
] |
ChemBL_V1
|
Low consensus scores, represented by a dark blue color, indicate more significant differences. (
|
[] |
ChemBL_V1
|
Common differentially expressed (DE) genes in pairwise comparisons of all HEK293 cells.
|
[] |
ChemBL_V1
|
Blue bars show number of DE genes in each pairwise comparison.
|
[] |
ChemBL_V1
|
Green bar shows 329 common DE genes in pairwise comparisons of progeny with HEK293 parental cells.
|
[] |
ChemBL_V1
|
Red bar shows common 38 DE genes in the comparison of suspension cells against adherent cells. (
|
[] |
ChemBL_V1
|
Top ten significant GO cellular components of the 329 common DE genes in pairwise comparisons between progeny cells and HEK293.
|
[
{
"end": 126,
"label": "CellLine",
"start": 120,
"text": "HEK293"
}
] |
ChemBL_V1
|
For further evaluation of the transcriptomic similarities and changes between HEK293 cell lines, pairwise differential expression comparisons between all cell lines were performed.
|
[
{
"end": 84,
"label": "CellLine",
"start": 78,
"text": "HEK293"
}
] |
ChemBL_V1
|
As expected, the parental cell line had the highest number of differentially expressed genes when compared to all other cell lines (Fig. 3b, Supplementary Fig. S5 and Supplementary Table S5).
|
[] |
ChemBL_V1
|
In addition, when looking at differentially expressed genes unique to certain comparisons, the largest group of genes were found common to all pairwise comparisons between HEK293 and each of the progeny cell lines (green bar in Fig. 3b), again emphasizing a relatively high degree of common transcriptomic changes amongst progeny cell lines differentiated from the parental HEK293.
|
[
{
"end": 178,
"label": "CellLine",
"start": 172,
"text": "HEK293"
},
{
"end": 380,
"label": "CellLine",
"start": 374,
"text": "HEK293"
}
] |
ChemBL_V1
|
As the progeny cell lines had an enrichment of differentially expressed genes associated with cellular component organization compared to HEK293, we sought to evaluate to what cellular compartments the 329 genes common to all pairwise comparisons between HEK293 and progeny cell lines localize.
|
[
{
"end": 144,
"label": "CellLine",
"start": 138,
"text": "HEK293"
},
{
"end": 261,
"label": "CellLine",
"start": 255,
"text": "HEK293"
}
] |
ChemBL_V1
|
In line with the overall differential expression evaluation (Fig. 3a), which emphasized changes in for instance cell adhesion and extracellular matrix organization, there was a significant (padj < 0.05) enrichment of genes relating to the integral compartment of plasma membrane (GO:0005887) amongst the common differentially expressed (DE) genes unique to the comparisons between HEK293 and all progeny cell lines (Fig. 3c).
|
[
{
"end": 387,
"label": "CellLine",
"start": 381,
"text": "HEK293"
}
] |
ChemBL_V1
|
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