Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
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4
INTRODUCTION
1
28
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
We, therefore, concluded that a better approach is to modify existing CPPs in order to search for peptides that may have enhanced intrinsic endosomolytic activity.
[ "28", "19", "21", "29" ]
163
700
0
false
We, therefore, concluded that a better approach is to modify existing CPPs in order to search for peptides that may have enhanced intrinsic endosomolytic activity.
[]
We, therefore, concluded that a better approach is to modify existing CPPs in order to search for peptides that may have enhanced intrinsic endosomolytic activity.
true
true
true
true
true
121
4
INTRODUCTION
1
28
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
Two vector strategies have been adopted, both taking into account the key roles played by Arg side chains in CPP uptake.
[ "28", "19", "21", "29" ]
120
701
0
false
Two vector strategies have been adopted, both taking into account the key roles played by Arg side chains in CPP uptake.
[]
Two vector strategies have been adopted, both taking into account the key roles played by Arg side chains in CPP uptake.
true
true
true
true
true
121
4
INTRODUCTION
1
28
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
We recently showed that (R-Ahx-R)4–PMO705 conjugate had significant splicing correction activity in the luciferase up-regulation model at 1 µM concentration in the absence of an endosomolytic agent (28).
[ "28", "19", "21", "29" ]
203
702
1
false
We recently showed that (R-Ahx-R)4–PMO705 conjugate had significant splicing correction activity in the luciferase up-regulation model at 1 µM concentration in the absence of an endosomolytic agent.
[ "28" ]
We recently showed that (R-Ahx-R)4–PMO705 conjugate had significant splicing correction activity in the luciferase up-regulation model at 1 µM concentration in the absence of an endosomolytic agent.
true
true
true
true
true
121
4
INTRODUCTION
1
19
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
Similarly we showed that a (R-Ahx-R)4–PNA705 conjugate also had significant splice correction activity at 1 µM concentration (19).
[ "28", "19", "21", "29" ]
130
703
1
false
Similarly we showed that a (R-Ahx-R)4–PNA705 conjugate also had significant splice correction activity at 1 µM concentration.
[ "19" ]
Similarly we showed that a (R-Ahx-R)4–PNA705 conjugate also had significant splice correction activity at 1 µM concentration.
true
true
true
true
true
121
4
INTRODUCTION
1
21
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
In parallel studies, we found substantial activity in an HIV-1 trans-activation inhibition assay (also requiring nuclear delivery) when a derivative of the known CPP Penetratin, in which six Arg residues were added to the N-terminus of the CPP, R6-Penetratin (R6Pen), was disulfide-conjugated to a PNA complementary to the trans-activation responsive element RNA (21).
[ "28", "19", "21", "29" ]
368
704
1
false
In parallel studies, we found substantial activity in an HIV-1 trans-activation inhibition assay (also requiring nuclear delivery) when a derivative of the known CPP Penetratin, in which six Arg residues were added to the N-terminus of the CPP, R6-Penetratin (R6Pen), was disulfide-conjugated to a PNA complementary to the trans-activation responsive element RNA.
[ "21" ]
In parallel studies, we found substantial activity in an HIV-1 trans-activation inhibition assay (also requiring nuclear delivery) when a derivative of the known CPP Penetratin, in which six Arg residues were added to the N-terminus of the CPP, R6-Penetratin (R6Pen), was disulfide-conjugated to a PNA complementary to the trans-activation responsive element RNA.
true
true
true
true
true
121
4
INTRODUCTION
1
28
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
We show now that this Arg-modified CPP when conjugated to a PNA targeted to the luciferase splice correction site shows by far the highest up-regulation of luciferase at both protein and RNA levels at 1 µM concentration compared to all previous CPPs studied.
[ "28", "19", "21", "29" ]
258
705
0
false
We show now that this Arg-modified CPP when conjugated to a PNA targeted to the luciferase splice correction site shows by far the highest up-regulation of luciferase at both protein and RNA levels at 1 µM concentration compared to all previous CPPs studied.
[]
We show now that this Arg-modified CPP when conjugated to a PNA targeted to the luciferase splice correction site shows by far the highest up-regulation of luciferase at both protein and RNA levels at 1 µM concentration compared to all previous CPPs studied.
true
true
true
true
true
121
4
INTRODUCTION
1
29
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
We also begin to characterize some aspects of the structure–function relationship and show that, for example, a W→L mutant that was reported to substantially reduce the cell penetration of Penetratin peptide (29) does not reduce the splice correction activity of the R6Pen–PNA conjugate.
[ "28", "19", "21", "29" ]
287
706
1
false
We also begin to characterize some aspects of the structure–function relationship and show that, for example, a W→L mutant that was reported to substantially reduce the cell penetration of Penetratin peptide does not reduce the splice correction activity of the R6Pen–PNA conjugate.
[ "29" ]
We also begin to characterize some aspects of the structure–function relationship and show that, for example, a W→L mutant that was reported to substantially reduce the cell penetration of Penetratin peptide does not reduce the splice correction activity of the R6Pen–PNA conjugate.
true
true
true
true
true
121
4
INTRODUCTION
1
28
[ "B28", "B19", "B21", "B29" ]
17,584,792
NA|pmid-17233600|pmid-16321967|NA
These results show that R6Pen might be a very good lead CPP towards further development of a suitable PNA–peptide conjugate candidate for in vivo studies.
[ "28", "19", "21", "29" ]
154
707
0
false
These results show that R6Pen might be a very good lead CPP towards further development of a suitable PNA–peptide conjugate candidate for in vivo studies.
[]
These results show that R6Pen might be a very good lead CPP towards further development of a suitable PNA–peptide conjugate candidate for in vivo studies.
true
true
true
true
true
121
0
DISCUSSION
1
19
[ "B19", "B28" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
The nuclear delivery of steric-block ON analogues conjugated with most CPPs for splice correction or exon skipping has been hampered by endosome trapping, unless an endosome disturbing drug or peptide is added, or high CPP–PNA conjugate concentrations are used.
[ "19", "28" ]
261
708
0
false
The nuclear delivery of steric-block ON analogues conjugated with most CPPs for splice correction or exon skipping has been hampered by endosome trapping, unless an endosome disturbing drug or peptide is added, or high CPP–PNA conjugate concentrations are used.
[]
The nuclear delivery of steric-block ON analogues conjugated with most CPPs for splice correction or exon skipping has been hampered by endosome trapping, unless an endosome disturbing drug or peptide is added, or high CPP–PNA conjugate concentrations are used.
true
true
true
true
true
122
0
DISCUSSION
1
19
[ "B19", "B28" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
Bearing in mind the key role played by cationic amino acids for CPP uptake, we have appended varying numbers of arginine residues to the N-terminal end of Penetratin, a CPP which by itself does not impart on the PNA a significant amount of splice correction ability.
[ "19", "28" ]
266
709
0
false
Bearing in mind the key role played by cationic amino acids for CPP uptake, we have appended varying numbers of arginine residues to the N-terminal end of Penetratin, a CPP which by itself does not impart on the PNA a significant amount of splice correction ability.
[]
Bearing in mind the key role played by cationic amino acids for CPP uptake, we have appended varying numbers of arginine residues to the N-terminal end of Penetratin, a CPP which by itself does not impart on the PNA a significant amount of splice correction ability.
true
true
true
true
true
122
0
DISCUSSION
1
19
[ "B19", "B28" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
R6Pen turned out to be the most active.
[ "19", "28" ]
39
710
0
false
R6Pen turned out to be the most active.
[]
R6Pen turned out to be the most active.
true
true
true
true
true
122
0
DISCUSSION
1
19
[ "B19", "B28" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
The level of activity obtained for splice correcting conjugated PNA is higher than for all other CPPs tested to date, including the recently described (R-Ahx-R)4 vector (19,28).
[ "19", "28" ]
177
711
0
false
The level of activity obtained for splice correcting conjugated PNA is higher than for all other CPPs tested to date, including the recently described (R-Ahx-R)4 vector.
[ "19,28" ]
The level of activity obtained for splice correcting conjugated PNA is higher than for all other CPPs tested to date, including the recently described (R-Ahx-R)4 vector.
true
true
true
true
true
122
0
DISCUSSION
1
19
[ "B19", "B28" ]
17,584,792
NA|NA|pmid-12613654|NA|pmid-16967918|NA|pmid-17233600|NA
Remarkably, R6Pen–PNA705 conjugates are highly active at 1 µM concentrations in the absence of any endosomolytic agents.
[ "19", "28" ]
120
712
0
false
Remarkably, R6Pen–PNA705 conjugates are highly active at 1 µM concentrations in the absence of any endosomolytic agents.
[]
Remarkably, R6Pen–PNA705 conjugates are highly active at 1 µM concentrations in the absence of any endosomolytic agents.
true
true
true
true
true
122
1
DISCUSSION
1
11
[ "B11", "B32" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
Quantification of luciferase expression, as carried out here and also in most published work to date, is a sensitive and convenient assay, which allows one to compare several conjugates quickly in terms of efficiency or specificity, and is thus the method of choice for structure–activity relationships studies.
[ "11", "32" ]
311
713
0
false
Quantification of luciferase expression, as carried out here and also in most published work to date, is a sensitive and convenient assay, which allows one to compare several conjugates quickly in terms of efficiency or specificity, and is thus the method of choice for structure–activity relationships studies.
[]
Quantification of luciferase expression, as carried out here and also in most published work to date, is a sensitive and convenient assay, which allows one to compare several conjugates quickly in terms of efficiency or specificity, and is thus the method of choice for structure–activity relationships studies.
true
true
true
true
true
123
1
DISCUSSION
1
11
[ "B11", "B32" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
However, such data are expressed in relative light units and do not allow direct determination of the extent to which aberrant splicing has been corrected.
[ "11", "32" ]
155
714
0
false
However, such data are expressed in relative light units and do not allow direct determination of the extent to which aberrant splicing has been corrected.
[]
However, such data are expressed in relative light units and do not allow direct determination of the extent to which aberrant splicing has been corrected.
true
true
true
true
true
123
1
DISCUSSION
1
11
[ "B11", "B32" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
RT-PCR products from the aberrantly and correctly spliced luciferase pre-mRNA can be separated easily by agarose gel electrophoresis, thus allowing evaluation of the extent of splice correction under various conditions.
[ "11", "32" ]
219
715
0
false
RT-PCR products from the aberrantly and correctly spliced luciferase pre-mRNA can be separated easily by agarose gel electrophoresis, thus allowing evaluation of the extent of splice correction under various conditions.
[]
RT-PCR products from the aberrantly and correctly spliced luciferase pre-mRNA can be separated easily by agarose gel electrophoresis, thus allowing evaluation of the extent of splice correction under various conditions.
true
true
true
true
true
123
1
DISCUSSION
1
11
[ "B11", "B32" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
RT-PCR data closely parallel luciferase luminescence measurements and indicate that the R6Pen-ss–PNA705 and the W→L variant allow sequence-specific splicing correction at 1 μM concentration to a high level (about 60–70%), whilst PNA705 alone or Pen-s-s–PNA705 are totally inactive.
[ "11", "32" ]
281
716
0
false
RT-PCR data closely parallel luciferase luminescence measurements and indicate that the R6Pen-ss–PNA705 and the W→L variant allow sequence-specific splicing correction at 1 μM concentration to a high level (about 60–70%), whilst PNA705 alone or Pen-s-s–PNA705 are totally inactive.
[]
RT-PCR data closely parallel luciferase luminescence measurements and indicate that the R6Pen-ss–PNA705 and the W→L variant allow sequence-specific splicing correction at 1 μM concentration to a high level (about 60–70%), whilst PNA705 alone or Pen-s-s–PNA705 are totally inactive.
true
true
true
true
true
123
1
DISCUSSION
1
11
[ "B11", "B32" ]
17,584,792
pmid-10807948|NA|pmid-15640444|pmid-17113327|pmid-9572837|NA
The levels of activity we have obtained (EC50 of 0.7–1.0 µM) now start to approach those obtained with the same assay by cationic lipid transfection using leashed PNA or other modified ON types (11,32).
[ "11", "32" ]
202
717
0
false
The levels of activity we have obtained (EC50 of 0.7–1.0 µM) now start to approach those obtained with the same assay by cationic lipid transfection using leashed PNA or other modified ON types.
[ "11,32" ]
The levels of activity we have obtained now start to approach those obtained with the same assay by cationic lipid transfection using leashed PNA or other modified ON types.
true
true
true
true
true
123
2
DISCUSSION
1
23
[ "B23" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
The achievement of a fair proportion of correction at low conjugate concentration is a key issue in the development of steric block ONs as potential therapeutics.
[ "23" ]
162
718
0
false
The achievement of a fair proportion of correction at low conjugate concentration is a key issue in the development of steric block ONs as potential therapeutics.
[]
The achievement of a fair proportion of correction at low conjugate concentration is a key issue in the development of steric block ONs as potential therapeutics.
true
true
true
true
true
124
2
DISCUSSION
1
23
[ "B23" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
By use of PI as an index of membrane permeabilization, we have indeed verified that R6Pen did not perturb membrane integrity of HeLa cells at the active dosage.
[ "23" ]
160
719
0
false
By use of PI as an index of membrane permeabilization, we have indeed verified that R6Pen did not perturb membrane integrity of HeLa cells at the active dosage.
[]
By use of PI as an index of membrane permeabilization, we have indeed verified that R6Pen did not perturb membrane integrity of HeLa cells at the active dosage.
true
true
true
true
true
124
2
DISCUSSION
1
23
[ "B23" ]
17,584,792
pmid-9572837|pmid-11574678|NA|pmid-15148357|pmid-16220989|pmid-16610796|NA|NA|pmid-17233600|NA
Previous studies from our group have established that high (>5 μM) concentrations of CPP–ON as R9 or K8–ON led to significant increase of PI uptake thus precluding further developments (23).
[ "23" ]
190
720
1
false
Previous studies from our group have established that high (>5 μM) concentrations of CPP–ON as R9 or K8–ON led to significant increase of PI uptake thus precluding further developments.
[ "23" ]
Previous studies from our group have established that high (>5 μM) concentrations of CPP–ON as R9 or K8–ON led to significant increase of PI uptake thus precluding further developments.
true
true
true
true
true
124
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
We have no explanation at this stage for the dramatically increased splice correction activity of R6Pen as compared to Pen or as compared to several Arg-rich CPPs.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
163
721
0
false
We have no explanation at this stage for the dramatically increased splice correction activity of R6Pen as compared to Pen or as compared to several Arg-rich CPPs.
[]
We have no explanation at this stage for the dramatically increased splice correction activity of R6Pen as compared to Pen or as compared to several Arg-rich CPPs.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
It is worth emphasizing in this respect that the W→L mutation in the Penetratin moiety, which is known to inhibit Penetratin peptide uptake (29), does not affect splice correction by R6Pen–PNA705 and instead gave rise to a slightly higher activity (Figures 6 and 7), thus inferring different mechanisms by which this CPP operates.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
330
722
1
false
It is worth emphasizing in this respect that the W→L mutation in the Penetratin moiety, which is known to inhibit Penetratin peptide uptake, does not affect splice correction by R6Pen–PNA705 and instead gave rise to a slightly higher activity (Figures 6 and 7), thus inferring different mechanisms by which this CPP operates.
[ "29" ]
It is worth emphasizing in this respect that the W→L mutation in the Penetratin moiety, which is known to inhibit Penetratin peptide uptake, does not affect splice correction by R6Pen–PNA705 and instead gave rise to a slightly higher activity (Figures 6 and 7), thus inferring different mechanisms by which this CPP operates.
true
true
true
true
true
125
3
DISCUSSION
1
19
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Along the same lines, chloroquine has a significantly lower effect on splice correction by R6Pen–PNA705 (Figure 3) as compared to Tat-PNA705 (19) or K8-PNA705 (23), in keeping with its improved intrinsic endosomal escape.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
221
723
1
false
Along the same lines, chloroquine has a significantly lower effect on splice correction by R6Pen–PNA705 (Figure 3) as compared to Tat-PNA705 or K8-PNA705, in keeping with its improved intrinsic endosomal escape.
[ "19", "23" ]
Along the same lines, chloroquine has a significantly lower effect on splice correction by R6Pen–PNA705 (Figure 3) as compared to Tat-PNA705 or K8-PNA705, in keeping with its improved intrinsic endosomal escape.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
We are also able to rule out significant effects of the Lys residues on the PNA part on splice correction activity.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
115
724
0
false
We are also able to rule out significant effects of the Lys residues on the PNA part on splice correction activity.
[]
We are also able to rule out significant effects of the Lys residues on the PNA part on splice correction activity.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Indeed we have found recently that R6Pen disulfide linked to a PNA 18-mer containing just one Lys residue on each end behaved identically to the corresponding conjugate containing four Lys residues (data not shown).
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
215
725
0
false
Indeed we have found recently that R6Pen disulfide linked to a PNA 18-mer containing just one Lys residue on each end behaved identically to the corresponding conjugate containing four Lys residues (data not shown).
[]
Indeed we have found recently that R6Pen disulfide linked to a PNA 18-mer containing just one Lys residue on each end behaved identically to the corresponding conjugate containing four Lys residues (data not shown).
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Further mechanistic studies are in progress, but it should be noted that we have deliberately avoided on these conjugates the use of fluorescent labels, which are commonly used to track cellular uptake by confocal microscopy.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
225
726
0
false
Further mechanistic studies are in progress, but it should be noted that we have deliberately avoided on these conjugates the use of fluorescent labels, which are commonly used to track cellular uptake by confocal microscopy.
[]
Further mechanistic studies are in progress, but it should be noted that we have deliberately avoided on these conjugates the use of fluorescent labels, which are commonly used to track cellular uptake by confocal microscopy.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Such labels alter the hydrophobicity of the conjugate at a particular region.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
77
727
0
false
Such labels alter the hydrophobicity of the conjugate at a particular region.
[]
Such labels alter the hydrophobicity of the conjugate at a particular region.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
This may alter the ability of the PNA-peptide to be released from endosomal compartments.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
89
728
0
false
This may alter the ability of the PNA-peptide to be released from endosomal compartments.
[]
This may alter the ability of the PNA-peptide to be released from endosomal compartments.
true
true
true
true
true
125
3
DISCUSSION
1
21
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Concerns about this have emerged recently in the case of our parallel studies on inhibition of HIV-1 Tat-dependent trans-activation (21).
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
137
729
1
false
Concerns about this have emerged recently in the case of our parallel studies on inhibition of HIV-1 Tat-dependent trans-activation.
[ "21" ]
Concerns about this have emerged recently in the case of our parallel studies on inhibition of HIV-1 Tat-dependent trans-activation.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
We have been unable so far to construct a conjugate that contains a fluorescein label on the PNA part of a R6-Penetratin–PNA conjugate targeted to TAR without losing all intra-nuclear inhibition activity in the absence of chloroquine in our HeLa cell assay (Turner, J.J., Arzumanov, A.A., Ivanova, G.D. and Gait, M.J., unpublished results).
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
340
730
0
false
We have been unable so far to construct a conjugate that contains a fluorescein label on the PNA part of a R6-Penetratin–PNA conjugate targeted to TAR without losing all intra-nuclear inhibition activity in the absence of chloroquine in our HeLa cell assay (Turner, J.J., Arzumanov, A.A., Ivanova, G.D. and Gait, M.J., unpublished results).
[]
We have been unable so far to construct a conjugate that contains a fluorescein label on the PNA part of a R6-Penetratin–PNA conjugate targeted to TAR without losing all intra-nuclear inhibition activity in the absence of chloroquine in our HeLa cell assay (Turner, J.J., Arzumanov, A.A., Ivanova, G.D. and Gait, M.J., unpublished results).
true
true
true
true
true
125
3
DISCUSSION
1
33
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Further, there does not appear to be a strong correlation of the amount of fluorescent oligonucleotide reagent seen to be taken up by cells and their biological activity (21,23,25,28), as has also become apparent in the design of lipid-based reagents for delivery of siRNA (33).
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
278
731
1
false
Further, there does not appear to be a strong correlation of the amount of fluorescent oligonucleotide reagent seen to be taken up by cells and their biological activity, as has also become apparent in the design of lipid-based reagents for delivery of siRNA.
[ "21,23,25,28", "33" ]
Further, there does not appear to be a strong correlation of the amount of fluorescent oligonucleotide reagent seen to be taken up by cells and their biological activity, as has also become apparent in the design of lipid-based reagents for delivery of siRNA.
true
true
true
true
true
125
3
DISCUSSION
1
29
[ "B29", "B19", "B23", "B21", "B21", "B23", "B25", "B28", "B33" ]
17,584,792
pmid-17233600|pmid-12411431|pmid-16321967|pmid-17154532|NA|NA|pmid-15533038|pmid-12411431|pmid-16321967|pmid-16125104|NA|NA|pmid-17233600|NA|pmid-14770178|pmid-17233600|NA|NA|pmid-17233600|NA|pmid-16321967|pmid-16321967|NA|pmid-15533038|NA|NA
Thus, more sophisticated ways of tracking locations of nucleic acids-based reagents and determining the precise compartments where activity takes place will be needed before such types of experiment become fully meaningful.
[ "29", "19", "23", "21", "21", "23", "25", "28", "33" ]
223
732
0
false
Thus, more sophisticated ways of tracking locations of nucleic acids-based reagents and determining the precise compartments where activity takes place will be needed before such types of experiment become fully meaningful.
[]
Thus, more sophisticated ways of tracking locations of nucleic acids-based reagents and determining the precise compartments where activity takes place will be needed before such types of experiment become fully meaningful.
true
true
true
true
true
125
4
DISCUSSION
0
null
null
17,584,792
NA|pmid-17233600|pmid-16321967|NA
Whether CPP delivery peptides and their cargoes should be conjugated through stable or unstable linkers has often been debated, but few direct comparisons have been provided.
null
174
733
0
false
null
null
Whether CPP delivery peptides and their cargoes should be conjugated through stable or unstable linkers has often been debated, but few direct comparisons have been provided.
true
true
true
true
true
126
4
DISCUSSION
0
null
null
17,584,792
NA|pmid-17233600|pmid-16321967|NA
In our case, a disulfide-linked conjugate was slightly (but reproducibly) more active than a stably conjugated PNA.
null
115
734
0
false
null
null
In our case, a disulfide-linked conjugate was slightly (but reproducibly) more active than a stably conjugated PNA.
true
true
true
true
true
126
4
DISCUSSION
0
null
null
17,584,792
NA|pmid-17233600|pmid-16321967|NA
Thus, we are now in the process of carrying out further more detailed structure–function analyses using such disulfide linkers to try to understand how the various parts of the R6-Penetratin peptide contribute to obtaining intra-nuclear splice correction activity.
null
264
735
0
false
null
null
Thus, we are now in the process of carrying out further more detailed structure–function analyses using such disulfide linkers to try to understand how the various parts of the R6-Penetratin peptide contribute to obtaining intra-nuclear splice correction activity.
true
true
true
true
true
126
4
DISCUSSION
0
null
null
17,584,792
NA|pmid-17233600|pmid-16321967|NA
The disulfide linker strategy may also be less susceptible to problems arising from steric interference by the conjugated delivery vehicle, or from potential non-specific binding of the vector to non-targeted entities.
null
218
736
0
false
null
null
The disulfide linker strategy may also be less susceptible to problems arising from steric interference by the conjugated delivery vehicle, or from potential non-specific binding of the vector to non-targeted entities.
true
true
true
true
true
126
4
DISCUSSION
0
null
null
17,584,792
NA|pmid-17233600|pmid-16321967|NA
However, use of PNA–peptide conjugates in vivo may require a more stable linkage and our work shows that a thioacetyl linker is also compatible with high-level splice correction activity.
null
187
737
0
false
null
null
However, use of PNA–peptide conjugates in vivo may require a more stable linkage and our work shows that a thioacetyl linker is also compatible with high-level splice correction activity.
true
true
true
true
true
126
5
DISCUSSION
1
34
[ "B34", "B35", "B36" ]
17,584,792
pmid-15104897|pmid-16724091|NA
The fact that strong splicing correction (as judged by the RT-PCR analysis) can be achieved at much lower (1 μM) concentration of the correcting ON than has previously proved possible opens up promising perspectives for in vivo applications.
[ "34", "35", "36" ]
241
738
0
false
The fact that strong splicing correction (as judged by the RT-PCR analysis) can be achieved at much lower (1 μM) concentration of the correcting ON than has previously proved possible opens up promising perspectives for in vivo applications.
[]
The fact that strong splicing correction (as judged by the RT-PCR analysis) can be achieved at much lower (1 μM) concentration of the correcting ON than has previously proved possible opens up promising perspectives for in vivo applications.
true
true
true
true
true
127
5
DISCUSSION
1
34
[ "B34", "B35", "B36" ]
17,584,792
pmid-15104897|pmid-16724091|NA
We hope that further optimization of the peptide–PNA construct will lead to a construct suitable for in vivo studies, and eventually for instance towards the treatment of disease-associated splicing defects [cancer, thalassemia, etc.
[ "34", "35", "36" ]
233
739
0
false
We hope that further optimization of the peptide–PNA construct will lead to a construct suitable for in vivo studies, and eventually for instance towards the treatment of disease-associated splicing defects [cancer, thalassemia, etc.
[]
We hope that further optimization of the peptide–PNA construct will lead to a construct suitable for in vivo studies, and eventually for instance towards the treatment of disease-associated splicing defects [cancer, thalassemia, etc.
true
true
true
true
true
127
5
DISCUSSION
1
34
[ "B34", "B35", "B36" ]
17,584,792
pmid-15104897|pmid-16724091|NA
(34)] or in exon-skipping strategies, as are now being considered for the treatment of Duchenne muscular dystrophy (35,36).
[ "34", "35", "36" ]
123
740
1
false
] or in exon-skipping strategies, as are now being considered for the treatment of Duchenne muscular dystrophy.
[ "34", "35,36" ]
] or in exon-skipping strategies, as are now being considered for the treatment of Duchenne muscular dystrophy.
false
false
true
true
false
127
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
The completion of a high-accuracy sequence of the human genome will enable significant advances in our understanding of disease-related genetic variation, both somatic and germ-line.
[ "1" ]
182
741
0
false
The completion of a high-accuracy sequence of the human genome will enable significant advances in our understanding of disease-related genetic variation, both somatic and germ-line.
[]
The completion of a high-accuracy sequence of the human genome will enable significant advances in our understanding of disease-related genetic variation, both somatic and germ-line.
true
true
true
true
true
128
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
Researchers are already using the human genome to study sequence variation in cell populations containing normal or abnormal DNA.
[ "1" ]
129
742
0
false
Researchers are already using the human genome to study sequence variation in cell populations containing normal or abnormal DNA.
[]
Researchers are already using the human genome to study sequence variation in cell populations containing normal or abnormal DNA.
true
true
true
true
true
128
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
Some of these studies have been designed to test hypotheses, for example, through linkage analysis that are concerned with the sequence variations at one locus or a small group of loci.
[ "1" ]
185
743
0
false
Some of these studies have been designed to test hypotheses, for example, through linkage analysis that are concerned with the sequence variations at one locus or a small group of loci.
[]
Some of these studies have been designed to test hypotheses, for example, through linkage analysis that are concerned with the sequence variations at one locus or a small group of loci.
true
true
true
true
true
128
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
Other studies have been designed to catalog variations across a wide selection of loci or genes, without a particular hypothesis to test, such as the HapMap project (1).
[ "1" ]
169
744
1
false
Other studies have been designed to catalog variations across a wide selection of loci or genes, without a particular hypothesis to test, such as the HapMap project.
[ "1" ]
Other studies have been designed to catalog variations across a wide selection of loci or genes, without a particular hypothesis to test, such as the HapMap project.
true
true
true
true
true
128
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
If the study focuses on genotyping samples using known variations, these genotyping approaches typically use microarray technology designed to detect hundreds of thousands of single nucleotide polymorphisms (SNPs), or PCR amplification using primers designed to test for a particular set of SNPs.
[ "1" ]
296
745
0
false
If the study focuses on genotyping samples using known variations, these genotyping approaches typically use microarray technology designed to detect hundreds of thousands of single nucleotide polymorphisms (SNPs), or PCR amplification using primers designed to test for a particular set of SNPs.
[]
If the study focuses on genotyping samples using known variations, these genotyping approaches typically use microarray technology designed to detect hundreds of thousands of single nucleotide polymorphisms (SNPs), or PCR amplification using primers designed to test for a particular set of SNPs.
true
true
true
true
true
128
0
INTRODUCTION
1
1
[ "b1" ]
17,088,289
pmid-16255080
However, when disease-causing somatic mutations are unknown, as is the current case for somatic mutations in nearly all types of cancer, re-sequencing is the state-of-the-art to discover new variations.
[ "1" ]
202
746
0
false
However, when disease-causing somatic mutations are unknown, as is the current case for somatic mutations in nearly all types of cancer, re-sequencing is the state-of-the-art to discover new variations.
[]
However, when disease-causing somatic mutations are unknown, as is the current case for somatic mutations in nearly all types of cancer, re-sequencing is the state-of-the-art to discover new variations.
true
true
true
true
true
128
1
INTRODUCTION
1
2
[ "b2", "b5" ]
17,088,289
pmid-16175573|pmid-15908952
Traditional sequencing technology applied to re-sequencing a particular genomic region (such as the exons of a gene) may also be used to detect known mutations.
[ "2", "5" ]
160
747
0
false
Traditional sequencing technology applied to re-sequencing a particular genomic region (such as the exons of a gene) may also be used to detect known mutations.
[]
Traditional sequencing technology applied to re-sequencing a particular genomic region (such as the exons of a gene) may also be used to detect known mutations.
true
true
true
true
true
129
1
INTRODUCTION
1
2
[ "b2", "b5" ]
17,088,289
pmid-16175573|pmid-15908952
However, because of its higher cost, re-sequencing is generally performed as a discovery tool to screen for new genomic sequence variations and mutations, including base substitutions, insertions and deletions.
[ "2", "5" ]
210
748
0
false
However, because of its higher cost, re-sequencing is generally performed as a discovery tool to screen for new genomic sequence variations and mutations, including base substitutions, insertions and deletions.
[]
However, because of its higher cost, re-sequencing is generally performed as a discovery tool to screen for new genomic sequence variations and mutations, including base substitutions, insertions and deletions.
true
true
true
true
true
129
1
INTRODUCTION
1
2
[ "b2", "b5" ]
17,088,289
pmid-16175573|pmid-15908952
In particular, gene re-sequencing efforts have recently been undertaken largely to catalog synonymous (not leading to amino acid substitutions) or non-synonymous (leading to amino acid substitutions) substitutions in genetic diseases, such as cancer (2–5).
[ "2", "5" ]
256
749
0
false
In particular, gene re-sequencing efforts have recently been undertaken largely to catalog synonymous (not leading to amino acid substitutions) or non-synonymous (leading to amino acid substitutions) substitutions in genetic diseases, such as cancer.
[ "2–5" ]
In particular, gene re-sequencing efforts have recently been undertaken largely to catalog synonymous (not leading to amino acid substitutions) or non-synonymous (leading to amino acid substitutions) substitutions in genetic diseases, such as cancer.
true
true
true
true
true
129
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
The Cancer Genome Atlas (TCGA) initiative proposed by the NIH is a large gene re-sequencing effort to take place over the next decade (NIH Press Release, December 13, 2005; available at ).
[ "6" ]
188
750
0
false
The Cancer Genome Atlas (TCGA) initiative proposed by the NIH is a large gene re-sequencing effort to take place over the next decade (NIH Press Release, December 13, 2005; available at ).
[]
The Cancer Genome Atlas (TCGA) initiative proposed by the NIH is a large gene re-sequencing effort to take place over the next decade (NIH Press Release, December 13, 2005; available at ).
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
TCGA will involve re-sequencing thousands of human genes from thousands of tumor samples.
[ "6" ]
89
751
0
false
TCGA will involve re-sequencing thousands of human genes from thousands of tumor samples.
[]
TCGA will involve re-sequencing thousands of human genes from thousands of tumor samples.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
Without major breakthroughs in sequencing technology, this effort will not be able to re-sequence all genes and will be limited to particular tumor types.
[ "6" ]
154
752
0
false
Without major breakthroughs in sequencing technology, this effort will not be able to re-sequence all genes and will be limited to particular tumor types.
[]
Without major breakthroughs in sequencing technology, this effort will not be able to re-sequence all genes and will be limited to particular tumor types.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
This large screening effort will naturally be followed by other smaller efforts undertaken by individual labs and small consortia to fill in the gaps, as well as to verify and validate putative variations on larger sample sizes.
[ "6" ]
228
753
0
false
This large screening effort will naturally be followed by other smaller efforts undertaken by individual labs and small consortia to fill in the gaps, as well as to verify and validate putative variations on larger sample sizes.
[]
This large screening effort will naturally be followed by other smaller efforts undertaken by individual labs and small consortia to fill in the gaps, as well as to verify and validate putative variations on larger sample sizes.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
A number of these smaller projects will be targeted at particular genes and at particular tumors.
[ "6" ]
97
754
0
false
A number of these smaller projects will be targeted at particular genes and at particular tumors.
[]
A number of these smaller projects will be targeted at particular genes and at particular tumors.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
In all of these projects, large and small, until sequencing costs drop by several orders of magnitude, funding limits will force decisions about which genes to re-sequence and in what order they will be examined.
[ "6" ]
212
755
0
false
In all of these projects, large and small, until sequencing costs drop by several orders of magnitude, funding limits will force decisions about which genes to re-sequence and in what order they will be examined.
[]
In all of these projects, large and small, until sequencing costs drop by several orders of magnitude, funding limits will force decisions about which genes to re-sequence and in what order they will be examined.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
Therefore, selection and prioritization of genes for re-sequencing is a common first step that will be repeated for each project.
[ "6" ]
129
756
0
false
Therefore, selection and prioritization of genes for re-sequencing is a common first step that will be repeated for each project.
[]
Therefore, selection and prioritization of genes for re-sequencing is a common first step that will be repeated for each project.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
With appreciable amounts of sequence and functional data available in public databases, and without tools to navigate these data, the gene selection process can become a painstaking task.
[ "6" ]
187
757
0
false
With appreciable amounts of sequence and functional data available in public databases, and without tools to navigate these data, the gene selection process can become a painstaking task.
[]
With appreciable amounts of sequence and functional data available in public databases, and without tools to navigate these data, the gene selection process can become a painstaking task.
true
true
true
true
true
130
2
INTRODUCTION
1
6
[ "b6" ]
17,088,289
pmid-16421597
The CancerGenes resource will keep up with the results produced by TCGA by utilizing the Catalogue of Somatic Mutations in Cancer (COSMIC) curated resource (6).
[ "6" ]
160
758
1
false
The CancerGenes resource will keep up with the results produced by TCGA by utilizing the Catalogue of Somatic Mutations in Cancer (COSMIC) curated resource.
[ "6" ]
The CancerGenes resource will keep up with the results produced by TCGA by utilizing the Catalogue of Somatic Mutations in Cancer (COSMIC) curated resource.
true
true
true
true
true
130
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
Our goal in creating the CancerGenes resource is to simplify the gene selection process commonly encountered in re-sequencing projects, and made difficult in large, geographically dispersed, collaborative groups.
[ "7", "8" ]
212
759
0
false
Our goal in creating the CancerGenes resource is to simplify the gene selection process commonly encountered in re-sequencing projects, and made difficult in large, geographically dispersed, collaborative groups.
[]
Our goal in creating the CancerGenes resource is to simplify the gene selection process commonly encountered in re-sequencing projects, and made difficult in large, geographically dispersed, collaborative groups.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
Our objective is to provide a resource that supports gene list storage, queries and comparisons.
[ "7", "8" ]
96
760
0
false
Our objective is to provide a resource that supports gene list storage, queries and comparisons.
[]
Our objective is to provide a resource that supports gene list storage, queries and comparisons.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
For example, a user of this resource could generate a superset of cancer-related genes listed in Hahn and Weinberg (7) and Vogelstein and Kinzler (8) by unioning these gene list sources, filter this list for tyrosine kinases and then intersect it with the user's own gene list.
[ "7", "8" ]
277
761
1
false
For example, a user of this resource could generate a superset of cancer-related genes listed in Hahn and Weinberg and Vogelstein and Kinzler by unioning these gene list sources, filter this list for tyrosine kinases and then intersect it with the user's own gene list.
[ "7", "8" ]
For example, a user of this resource could generate a superset of cancer-related genes listed in Hahn and Weinberg and Vogelstein and Kinzler by unioning these gene list sources, filter this list for tyrosine kinases and then intersect it with the user's own gene list.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
Because of our interests, we have initially focused on cancer genome re-sequencing projects, such as TCGA.
[ "7", "8" ]
106
762
0
false
Because of our interests, we have initially focused on cancer genome re-sequencing projects, such as TCGA.
[]
Because of our interests, we have initially focused on cancer genome re-sequencing projects, such as TCGA.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
A key requirement for rational, high quality gene selection and prioritization is aggregation of up-to-date gene-centric information, addition of information by domain experts and summarization.
[ "7", "8" ]
194
763
0
false
A key requirement for rational, high quality gene selection and prioritization is aggregation of up-to-date gene-centric information, addition of information by domain experts and summarization.
[]
A key requirement for rational, high quality gene selection and prioritization is aggregation of up-to-date gene-centric information, addition of information by domain experts and summarization.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
Therefore, we automated the data aggregation process, provided a mechanism to add information from domain experts, such as researchers with intimate knowledge of the importance of particular gene sets in certain disease processes, and wrote software to provide convenient web access to frequently updated information.
[ "7", "8" ]
317
764
0
false
Therefore, we automated the data aggregation process, provided a mechanism to add information from domain experts, such as researchers with intimate knowledge of the importance of particular gene sets in certain disease processes, and wrote software to provide convenient web access to frequently updated information.
[]
Therefore, we automated the data aggregation process, provided a mechanism to add information from domain experts, such as researchers with intimate knowledge of the importance of particular gene sets in certain disease processes, and wrote software to provide convenient web access to frequently updated information.
true
true
true
true
true
131
3
INTRODUCTION
1
7
[ "b7", "b8" ]
17,088,289
pmid-12044009|pmid-15286780
In addition, since lists of genes are a common end-point of many high-throughput studies, such as gene expression profiling using microarrays, we believe this resource will be a useful adjunct to a wide range of cancer-relevant studies outside the scope of gene re-sequencing.
[ "7", "8" ]
276
765
0
false
In addition, since lists of genes are a common end-point of many high-throughput studies, such as gene expression profiling using microarrays, we believe this resource will be a useful adjunct to a wide range of cancer-relevant studies outside the scope of gene re-sequencing.
[]
In addition, since lists of genes are a common end-point of many high-throughput studies, such as gene expression profiling using microarrays, we believe this resource will be a useful adjunct to a wide range of cancer-relevant studies outside the scope of gene re-sequencing.
true
true
true
true
true
131
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
CancerGenes is a gene list-centric resource, with its intended niche being cancer-associated gene selection and prioritization through aggregation of relevant information, logical operations on lists, selection options and summary presentation.
null
244
766
0
false
null
null
CancerGenes is a gene list-centric resource, with its intended niche being cancer-associated gene selection and prioritization through aggregation of relevant information, logical operations on lists, selection options and summary presentation.
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
This is in contrast to the large number of bioinformatics resources that support gene-centric queries and retrieve aggregated gene-centric information, or support genome sequence browsing.
null
188
767
0
false
null
null
This is in contrast to the large number of bioinformatics resources that support gene-centric queries and retrieve aggregated gene-centric information, or support genome sequence browsing.
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
In fact, we have retrieved data from a number of these gene-centric resources (e.g.
null
83
768
0
false
null
null
In fact, we have retrieved data from a number of these gene-centric resources (e.g.
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
NCBI Entrez Gene, Ensembl BioMart, Sanger COSMIC).
null
50
769
0
false
null
null
NCBI Entrez Gene, Ensembl BioMart, Sanger COSMIC).
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
However, as CancerGenes's intended user population deals in gene lists, rather than individual gene records, we have focused on gene list-based functionalities, such as union and intersection set operations, rather than single gene-based queries.
null
246
770
0
false
null
null
However, as CancerGenes's intended user population deals in gene lists, rather than individual gene records, we have focused on gene list-based functionalities, such as union and intersection set operations, rather than single gene-based queries.
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
In addition, we have preloaded lists of genes that we anticipate our target audience will find useful, including list provided by domain experts.
null
145
771
0
false
null
null
In addition, we have preloaded lists of genes that we anticipate our target audience will find useful, including list provided by domain experts.
true
true
true
true
true
132
0
DISCUSSION
0
null
null
17,088,289
pmid-16255080
In addition to the list-centric operations, as all active human genes from Entrez Gene are included in CancerGenes, and as it supports a number of use cases, projects that requires gene-centric data may also find this resource useful.
null
234
772
0
false
null
null
In addition to the list-centric operations, as all active human genes from Entrez Gene are included in CancerGenes, and as it supports a number of use cases, projects that requires gene-centric data may also find this resource useful.
true
true
true
true
true
132
1
DISCUSSION
0
null
null
17,088,289
pmid-16175573|pmid-15908952
Because of our interest in cancer, we have loaded cancer-focused data and lists into CancerGenes.
null
97
773
0
false
null
null
Because of our interest in cancer, we have loaded cancer-focused data and lists into CancerGenes.
true
true
true
true
true
133
1
DISCUSSION
0
null
null
17,088,289
pmid-16175573|pmid-15908952
It is our desire to support cancer genome sequencing projects, such as the TGCA with this resource.
null
99
774
0
false
null
null
It is our desire to support cancer genome sequencing projects, such as the TGCA with this resource.
true
true
true
true
true
133
1
DISCUSSION
0
null
null
17,088,289
pmid-16175573|pmid-15908952
However, there is no reason why CancerGenes could not support other re-sequencing projects, which target other diseases with a genetic component.
null
145
775
0
false
null
null
However, there is no reason why CancerGenes could not support other re-sequencing projects, which target other diseases with a genetic component.
true
true
true
true
true
133
2
DISCUSSION
0
null
null
17,088,289
pmid-16421597
Our intent with the four types of preloaded gene lists—Cancer review, Cellmap.org Pathways, Entrez query and Sanger CGC—was to cover all genes likely to be related to cancer through mutation.
null
191
776
0
false
null
null
Our intent with the four types of preloaded gene lists—Cancer review, Cellmap.org Pathways, Entrez query and Sanger CGC—was to cover all genes likely to be related to cancer through mutation.
true
true
true
true
true
134
2
DISCUSSION
0
null
null
17,088,289
pmid-16421597
Table 7 shows the sizes and numbers of genes resulting from set intersection (overlap) and union operations between these four types of preloaded gene lists.
null
157
777
0
false
null
null
Table 7 shows the sizes and numbers of genes resulting from set intersection (overlap) and union operations between these four types of preloaded gene lists.
true
true
true
true
true
134
2
DISCUSSION
0
null
null
17,088,289
pmid-16421597
Most relative overlaps between lists (i.e.
null
42
778
0
false
null
null
Most relative overlaps between lists (i.e.
true
true
true
true
true
134
2
DISCUSSION
0
null
null
17,088,289
pmid-16421597
intersection size divided by union size) are ∼10%, with the exception of the overlap between Cancer review and Sanger CGC, which is 83%.
null
136
779
0
false
null
null
intersection size divided by union size) are ∼10%, with the exception of the overlap between Cancer review and Sanger CGC, which is 83%.
false
true
true
true
false
134
2
DISCUSSION
0
null
null
17,088,289
pmid-16421597
We are not surprised by these results, because of our criteria used to generate each list (see Materials and Methods and Tables 4 and 5).
null
137
780
0
false
null
null
We are not surprised by these results, because of our criteria used to generate each list (see Materials and Methods and Tables 4 and 5).
true
true
true
true
true
134
3
DISCUSSION
0
null
null
17,088,289
pmid-12044009|pmid-15286780
There are a total of 2274 unique genes in our preloaded lists, which means annotation coverage of all 39 250 genes in CancerGenes is 5.8%.
null
138
781
0
false
null
null
There are a total of 2274 unique genes in our preloaded lists, which means annotation coverage of all 39 250 genes in CancerGenes is 5.8%.
true
true
true
true
true
135
3
DISCUSSION
0
null
null
17,088,289
pmid-12044009|pmid-15286780
If the Sanger CGC list is considered definitive in regard to current state of knowledge about mutated genes in cancer, then 15% (344/2274) of this 5.8% is known to be due to mutation.
null
183
782
0
false
null
null
If the Sanger CGC list is considered definitive in regard to current state of knowledge about mutated genes in cancer, then 15% (344/2274) of this 5.8% is known to be due to mutation.
true
true
true
true
true
135
3
DISCUSSION
0
null
null
17,088,289
pmid-12044009|pmid-15286780
Confirmation of a mutation-based association to cancer for the remaining 85% of genes in our preloaded lists (and ∼5% of all genes), will have to await the conclusion of the many cancer genome sequencing initiatives.
null
216
783
0
false
null
null
Confirmation of a mutation-based association to cancer for the remaining 85% of genes in our preloaded lists (and ∼5% of all genes), will have to await the conclusion of the many cancer genome sequencing initiatives.
true
true
true
true
true
135
4
DISCUSSION
0
null
null
17,088,289
null
CancerGenes consolidates information from several gene-centric resources of use to those embarking on gene re-sequencing efforts large or small.
null
144
784
0
false
null
null
CancerGenes consolidates information from several gene-centric resources of use to those embarking on gene re-sequencing efforts large or small.
true
true
true
true
true
136
4
DISCUSSION
0
null
null
17,088,289
null
Our focus in developing this resource has been on simple gene list-centric query tools and the tabular display of information.
null
126
785
0
false
null
null
Our focus in developing this resource has been on simple gene list-centric query tools and the tabular display of information.
true
true
true
true
true
136
4
DISCUSSION
0
null
null
17,088,289
null
The simple and flexible architecture we have developed for storing and annotating gene lists will allow us to keep pace with the currently rapid development of gene lists, sets and signatures, and provide an up-to-date resource for our users.
null
242
786
0
false
null
null
The simple and flexible architecture we have developed for storing and annotating gene lists will allow us to keep pace with the currently rapid development of gene lists, sets and signatures, and provide an up-to-date resource for our users.
true
true
true
true
true
136
0
INTRODUCTION
1
1
[ "b1" ]
17,142,240
NA
Classification of proteins is a fundamental technique in computational genomics which is carried out, to a large extent, by automated machine learning methods (1).
[ "1" ]
163
787
1
false
Classification of proteins is a fundamental technique in computational genomics which is carried out, to a large extent, by automated machine learning methods.
[ "1" ]
Classification of proteins is a fundamental technique in computational genomics which is carried out, to a large extent, by automated machine learning methods.
true
true
true
true
true
137
0
INTRODUCTION
1
1
[ "b1" ]
17,142,240
NA
Application of machine learning techniques to proteins is a delicate task since the known protein groups—such as those of domain-types and protein families—are highly variable in most of their characteristics (e.g.
[ "1" ]
214
788
0
false
Application of machine learning techniques to proteins is a delicate task since the known protein groups—such as those of domain-types and protein families—are highly variable in most of their characteristics (e.g.
[]
Application of machine learning techniques to proteins is a delicate task since the known protein groups—such as those of domain-types and protein families—are highly variable in most of their characteristics (e.g.
true
true
true
true
true
137
0
INTRODUCTION
1
1
[ "b1" ]
17,142,240
NA
average sequence length, number of known members, within-group similarity, etc.
[ "1" ]
79
789
0
false
average sequence length, number of known members, within-group similarity, etc.
[]
average sequence length, number of known members, within-group similarity, etc.
false
true
true
true
false
137
0
INTRODUCTION
1
1
[ "b1" ]
17,142,240
NA
A further problem is the complexity of the calculations, since a system capable of testing and comparing machine learning algorithms should include (i) datasets and classification tasks; (ii) sequence/structure comparison methods; (iii) classification algorithms; and (iv) a validation protocol.
[ "1" ]
295
790
0
false
A further problem is the complexity of the calculations, since a system capable of testing and comparing machine learning algorithms should include (i) datasets and classification tasks; (ii) sequence/structure comparison methods; (iii) classification algorithms; and (iv) a validation protocol.
[]
A further problem is the complexity of the calculations, since a system capable of testing and comparing machine learning algorithms should include (i) datasets and classification tasks; (ii) sequence/structure comparison methods; (iii) classification algorithms; and (iv) a validation protocol.
true
true
true
true
true
137
1
INTRODUCTION
0
null
null
17,142,240
null
Even though the application of machine learning algorithms to protein classification is a frequent topic in the literature, it is often quite difficult to compare the performance of a new classification method with the figures published on other methods.
null
254
791
0
false
null
null
Even though the application of machine learning algorithms to protein classification is a frequent topic in the literature, it is often quite difficult to compare the performance of a new classification method with the figures published on other methods.
true
true
true
true
true
138
1
INTRODUCTION
0
null
null
17,142,240
null
In our opinion this is mainly because (i) the published results are often based on different and sometimes by then obsolete databases and program versions, (ii) the fine-tuning of the program parameters is sometimes not described in sufficient detail and finally, (iii) the classification performance is characterized by various, often ad hoc chosen performance measures and validation protocols.
null
396
792
0
false
null
null
In our opinion this is mainly because (i) the published results are often based on different and sometimes by then obsolete databases and program versions, (ii) the fine-tuning of the program parameters is sometimes not described in sufficient detail and finally, (iii) the classification performance is characterized by various, often ad hoc chosen performance measures and validation protocols.
true
true
true
true
true
138
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
In order to get a reliable estimate of the performance, an algorithm needs to be tested on not only one, but many protein groups selected from a well-curated database.
[ "2", "4" ]
167
793
0
false
In order to get a reliable estimate of the performance, an algorithm needs to be tested on not only one, but many protein groups selected from a well-curated database.
[]
In order to get a reliable estimate of the performance, an algorithm needs to be tested on not only one, but many protein groups selected from a well-curated database.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
For instance, an algorithm may be efficient in classifying protein superfamilies into families, but less efficient in classifying folds into superfamilies.
[ "2", "4" ]
155
794
0
false
For instance, an algorithm may be efficient in classifying protein superfamilies into families, but less efficient in classifying folds into superfamilies.
[]
For instance, an algorithm may be efficient in classifying protein superfamilies into families, but less efficient in classifying folds into superfamilies.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
In other words, one can choose to conduct a test at different levels of a classification hierarchy, and within each of these levels one can define many different classification tasks.
[ "2", "4" ]
183
795
0
false
In other words, one can choose to conduct a test at different levels of a classification hierarchy, and within each of these levels one can define many different classification tasks.
[]
In other words, one can choose to conduct a test at different levels of a classification hierarchy, and within each of these levels one can define many different classification tasks.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
The choice of the test/train groups is also critical.
[ "2", "4" ]
53
796
0
false
The choice of the test/train groups is also critical.
[]
The choice of the test/train groups is also critical.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
It is well known that once a group of proteins has been identified, it is relatively easy to recognize new members of the group.
[ "2", "4" ]
128
797
0
false
It is well known that once a group of proteins has been identified, it is relatively easy to recognize new members of the group.
[]
It is well known that once a group of proteins has been identified, it is relatively easy to recognize new members of the group.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
On the other hand, each new genome may contain new subtypes of the already known groups (say new families within a known superfamily), which are often not recognized by the classification algorithms trained on the old examples.
[ "2", "4" ]
227
798
0
false
On the other hand, each new genome may contain new subtypes of the already known groups (say new families within a known superfamily), which are often not recognized by the classification algorithms trained on the old examples.
[]
On the other hand, each new genome may contain new subtypes of the already known groups (say new families within a known superfamily), which are often not recognized by the classification algorithms trained on the old examples.
true
true
true
true
true
139
2
INTRODUCTION
1
2
[ "b2", "b4" ]
17,142,240
pmid-14980014|pmid-10890390
In other words, it is important to know how a given algorithm generalizes to novel subtypes.
[ "2", "4" ]
92
799
0
false
In other words, it is important to know how a given algorithm generalizes to novel subtypes.
[]
In other words, it is important to know how a given algorithm generalizes to novel subtypes.
true
true
true
true
true
139