Experiment / E585KN2J7Integrated lentiMPRA

HEK293 conformation-locking mutagenesis MPRA of RNA switches

A systematic search for RNA structural switches across the human transcriptome

A second lentiviral MPRA library tested four designed mutations per candidate RNA switch, with two perturbations favoring each of two predicted mutually exclusive RNA conformations. The same two-replicate, eight-bin HEK293 eGFP:mCherry sorting and genomic-DNA/RNA sequencing design quantified conformation-dependent reporter activity.

Processed tables are specific to each experiment. Column names, units, measurements, and table structure are not standardized across the database. Check this experiment’s column definitions and quality-control notes before comparing or combining data.

Perturbation & assay details

Basal / Untreated

Designed stem-strengthening and stem-weakening substitutions were introduced to shift the RNA ensemble toward conformation 1 or 2. Constructs were cloned into the same dual eGFP–mCherry 3′UTR lentiviral reporter, transduced at low MOI, sorted into eight equal eGFP:mCherry bins, and quantified from paired genomic-DNA and RNA libraries.

Processed data

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Filters apply to this table only. The CSV download contains the complete processed table; filtered rows are available through the API.

Column dictionary · 73 definitions
element_id
Source RNA switch fragment identifier.
candidate_id
Unique candidate identifier combining element_id and the source SwitchFinder score; disambiguates repeated fragment names with distinct predictions.
construct_id
Unique construct identifier combining candidate_id and the mutation perturbation.
transcript_id
Ensembl transcript identifier parsed from element_id.
fragment_index
Overlapping 186-nt 3′UTR fragment index parsed from element_id.
perturbation
Source mutation design: strengthen or weaken conformation 1 or 2.
mutation_target_conformation
Predicted conformation favored by the perturbation, 1 or 2.
mutation_mode
Mutation strategy: strengthen or weaken the target conformation-specific stem.
sequence
DNA sequence of the designed mutant tested in the reporter.
sequence_length_bp
Length of the tested sequence in base pairs.
gc_fraction
Fraction of sequence bases that are G or C.
switchfinder_score
Source SwitchFinder RNA-switch score.
is_published_high_confidence_switch
Source RNA switch flag; true identifies the 245 switches reported as final high-confidence switches.
candidate_variant_count
Number of perturbation constructs in the retained candidate group; four expected.
candidate_complete_qc
True when all four expected perturbations for this candidate passed QC.
dna_r1_b1_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 1.
dna_r1_b2_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 2.
dna_r1_b3_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 3.
dna_r1_b4_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 4.
dna_r1_b5_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 5.
dna_r1_b6_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 6.
dna_r1_b7_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 7.
dna_r1_b8_count
Source genomic-DNA read-count value for biological replicate 1, FACS expression bin 8.
dna_r2_b1_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 1.
dna_r2_b2_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 2.
dna_r2_b3_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 3.
dna_r2_b4_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 4.
dna_r2_b5_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 5.
dna_r2_b6_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 6.
dna_r2_b7_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 7.
dna_r2_b8_count
Source genomic-DNA read-count value for biological replicate 2, FACS expression bin 8.
rna_r1_b1_count
Source RNA read-count value for biological replicate 1, FACS expression bin 1.
rna_r1_b2_count
Source RNA read-count value for biological replicate 1, FACS expression bin 2.
rna_r1_b3_count
Source RNA read-count value for biological replicate 1, FACS expression bin 3.
rna_r1_b4_count
Source RNA read-count value for biological replicate 1, FACS expression bin 4.
rna_r1_b5_count
Source RNA read-count value for biological replicate 1, FACS expression bin 5.
rna_r1_b6_count
Source RNA read-count value for biological replicate 1, FACS expression bin 6.
rna_r1_b7_count
Source RNA read-count value for biological replicate 1, FACS expression bin 7.
rna_r1_b8_count
Source RNA read-count value for biological replicate 1, FACS expression bin 8.
rna_r2_b1_count
Source RNA read-count value for biological replicate 2, FACS expression bin 1.
rna_r2_b2_count
Source RNA read-count value for biological replicate 2, FACS expression bin 2.
rna_r2_b3_count
Source RNA read-count value for biological replicate 2, FACS expression bin 3.
rna_r2_b4_count
Source RNA read-count value for biological replicate 2, FACS expression bin 4.
rna_r2_b5_count
Source RNA read-count value for biological replicate 2, FACS expression bin 5.
rna_r2_b6_count
Source RNA read-count value for biological replicate 2, FACS expression bin 6.
rna_r2_b7_count
Source RNA read-count value for biological replicate 2, FACS expression bin 7.
rna_r2_b8_count
Source RNA read-count value for biological replicate 2, FACS expression bin 8.
gdna_total_rep1
Sum of source genomic-DNA values across bins 1–8 for replicate 1, on the source count scale.
rna_total_rep1
Sum of source RNA values across bins 1–8 for replicate 1, on the source count scale.
normalized_gdna_total_rep1
Median-of-ratios normalized genomic-DNA total for replicate 1.
normalized_rna_total_rep1
Median-of-ratios normalized RNA total for replicate 1.
activity_log2_rna_dna_rep1
Log2 of normalized RNA total divided by normalized genomic-DNA total for replicate 1, using a 0.5 pseudocount.
mean_rna_expression_bin_rep1
RNA-count-weighted mean FACS bin number (1–8) for replicate 1.
dna_adjusted_expression_bin_rep1
Mean FACS bin number weighted by per-bin normalized RNA/genomic-DNA enrichment for replicate 1, with 0.5 pseudocounts.
gdna_total_rep2
Sum of source genomic-DNA values across bins 1–8 for replicate 2, on the source count scale.
rna_total_rep2
Sum of source RNA values across bins 1–8 for replicate 2, on the source count scale.
normalized_gdna_total_rep2
Median-of-ratios normalized genomic-DNA total for replicate 2.
normalized_rna_total_rep2
Median-of-ratios normalized RNA total for replicate 2.
activity_log2_rna_dna_rep2
Log2 of normalized RNA total divided by normalized genomic-DNA total for replicate 2, using a 0.5 pseudocount.
mean_rna_expression_bin_rep2
RNA-count-weighted mean FACS bin number (1–8) for replicate 2.
dna_adjusted_expression_bin_rep2
Mean FACS bin number weighted by per-bin normalized RNA/genomic-DNA enrichment for replicate 2, with 0.5 pseudocounts.
activity_log2_rna_dna
Mean of the two replicate log2 RNA/genomic-DNA activity values.
activity_log2_rna_dna_sd
Sample standard deviation of the two replicate log2 RNA/genomic-DNA activity values.
activity_log2_rna_dna_rep2_minus_rep1
Replicate 2 minus replicate 1 log2 RNA/genomic-DNA activity.
mean_rna_expression_bin
Mean of the two RNA-weighted mean FACS-bin scores.
dna_adjusted_expression_bin
Mean of the two DNA-adjusted expression-bin scores.
expression_bin_score_rep2_minus_rep1
Replicate 2 minus replicate 1 RNA-weighted mean-bin score.
replicate_bin_profile_pearson_r
Pearson correlation between the two replicate per-bin RNA/genomic-DNA enrichment profiles.
candidate_conformation_1_mean_activity
Mean activity_log2_rna_dna across the two retained perturbations favoring conformation 1 for this candidate.
candidate_conformation_2_mean_activity
Mean activity_log2_rna_dna across the two retained perturbations favoring conformation 2 for this candidate.
candidate_conformation_2_minus_conformation_1_activity
Candidate-level conformation 2 mean activity minus conformation 1 mean activity; repeated on each variant row.
variant_activity_vs_target_conformation_mean
This variant's activity minus the mean activity of the other perturbation targeting the same conformation.
variant_activity_vs_opposite_conformation_mean
This variant's activity minus the mean activity of the two perturbations targeting the opposite conformation.

Quality control

Author workflow retained: approximately 20% low-MOI lentiviral infection; eight equal 12.5% FACS bins; two biological replicates; cutadapt trimming, UMI handling, BWA-MEM mapping, featureCounts quantification, median-of-ratios normalization, and replicate/candidate ranking. Additional package QC required valid A/C/G/T sequence and at least 100 source values summed across all eight bins for both RNA and genomic DNA in each replicate. Only complete four-perturbation candidate groups were retained. 5116/5128 construct rows (1279 candidate score groups) passed.

Curation notes

Source: GSE266058 mutagenesis_screen.tsv.gz (publisher Supplementary Data S5); the complete source matrix is preserved in raw_data. The public table has four perturbation rows per candidate score group and no individual barcode identifiers. candidate_id combines RNA switch name and SwitchFinder score because some fragment names occur with more than one prediction. The source RNA switch TRUE/FALSE flag is retained as is_published_high_confidence_switch; after QC, 244 high-confidence candidate groups remain. Source bin values are retained; derived activity and bin scores use the same median-of-ratios and pseudocount calculation documented for the functional screen. A positive candidate_conformation_2_minus_conformation_1_activity means the perturbations favoring conformation 2 had higher reporter RNA/DNA activity on average.

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