Experiment / E155IUZ3QIntegrated lentiMPRA

Seven-time-point perturbation lentiMPRA during human ESC neural differentiation

Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation

A 10,041-sequence integrated lentiMPRA library containing wild-type, scrambled/random-control, and single- or double-motif perturbation constructs was assayed at 0, 3, 6, 12, 24, 48, and 72 hours after dual-SMAD neural induction of H1 human embryonic stem cells. This package table contains the 598 consensus functional regulatory sites (FRSs) retained by the authors' cross-method perturbation QC.

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

Dual-SMAD inhibition to induce neural differentiation; samples collected at 0, 3, 6, 12, 24, 48, and 72 hours after induction

The library contained 591 endogenous 171-bp human regulatory regions and 2,144 selected motif instances, with three motif-perturbation designs plus selected double perturbations, 591 WT controls, 591 SCRAM controls, and RAND controls. Constructs were cloned upstream of a minimal promoter in a pLS-SceI-derived lentiMPRA vector with 15-bp random 5-prime UTR EGFP barcodes, packaged as lentivirus, and infected into H1/WA-01 hESCs at MOI 5–8. Three independent replicate cultures were used; two received one lentivirus batch and one received a second batch. Integrated DNA barcodes and transcribed RNA barcodes were quantified at seven time points, and MPRAflow/MPRAnalyze were used to assign barcodes, estimate alpha activity, and test WT versus PERT effects.

Processed data

50 rows per page. Click a cell to inspect its full value.

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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 · 53 definitions
frs_id
Stable package identifier for the consensus functional regulatory site row.
motif_id
Motif/PWM identifier for the perturbed binding site.
transcription_factor
TF token parsed from the motif identifier before the first underscore.
region
The 171-bp endogenous regulatory region, reported as chromosome:start-end in hg19 coordinates.
chromosome
Chromosome parsed from region.
region_start_hg19
Reported hg19 region start coordinate.
region_end_hg19
Reported hg19 region end coordinate.
motif_effect_code
Source effect code: 1 essential, 2 contributing, 3 silencing, 4 inhibiting.
motif_effect_category
Published FRS category based on the effect of motif perturbation.
effect_direction
Direction of the perturbation contrast: activating motifs have positive WT-over-PERT effects; dampening motifs have negative WT-over-PERT effects.
motif_start_1based
1-based start position of the motif within the tested 171-bp sequence.
motif_end_1based
1-based end position of the motif within the tested 171-bp sequence.
strand
Motif strand in the tested sequence (+ or -).
replaced_sequence
Replacement sequence used to perturb the motif.
closest_genes
Semicolon-separated closest genes within 1 Mb, normalized from the source comma-delimited field.
temporal_cluster_wt
Source temporal cluster label (1–4) for the WT region.
temporal_cluster_log2fc
Source temporal cluster label (1–4) for the log2 fold-change trajectory.
temporal_cluster_wt_alpha
Source temporal cluster label (1–4) for the WT alpha trajectory.
pchiC_hESC_genes
Semicolon-separated PCHi-C-linked genes in hESCs, where available.
pchiC_NPC_genes
Semicolon-separated PCHi-C-linked genes in neural progenitor cells, where available.
pchiC_excitatory_genes
Semicolon-separated PCHi-C-linked genes in excitatory neurons, where available.
pchiC_hippocampal_genes
Semicolon-separated PCHi-C-linked genes in hippocampal cells, where available.
pchiC_motor_genes
Semicolon-separated PCHi-C-linked genes in motor neurons, where available.
pchiC_astrocytes_genes
Semicolon-separated PCHi-C-linked genes in astrocytes, where available.
log2_wt_over_perturbed_0h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 0 hours.
log2_wt_over_perturbed_3h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 3 hours.
log2_wt_over_perturbed_6h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 6 hours.
log2_wt_over_perturbed_12h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 12 hours.
log2_wt_over_perturbed_24h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 24 hours.
log2_wt_over_perturbed_48h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 48 hours.
log2_wt_over_perturbed_72h
Published MPRAnalyze log2 fold-change for WT activity divided by perturbed activity at 72 hours.
wt_activity_alpha_0h
MPRAnalyze WT sequence activity alpha at 0 hours.
wt_activity_alpha_3h
MPRAnalyze WT sequence activity alpha at 3 hours.
wt_activity_alpha_6h
MPRAnalyze WT sequence activity alpha at 6 hours.
wt_activity_alpha_12h
MPRAnalyze WT sequence activity alpha at 12 hours.
wt_activity_alpha_24h
MPRAnalyze WT sequence activity alpha at 24 hours.
wt_activity_alpha_48h
MPRAnalyze WT sequence activity alpha at 48 hours.
wt_activity_alpha_72h
MPRAnalyze WT sequence activity alpha at 72 hours.
perturbed_activity_alpha_0h
MPRAnalyze motif-perturbed sequence activity alpha at 0 hours.
perturbed_activity_alpha_3h
MPRAnalyze motif-perturbed sequence activity alpha at 3 hours.
perturbed_activity_alpha_6h
MPRAnalyze motif-perturbed sequence activity alpha at 6 hours.
perturbed_activity_alpha_12h
MPRAnalyze motif-perturbed sequence activity alpha at 12 hours.
perturbed_activity_alpha_24h
MPRAnalyze motif-perturbed sequence activity alpha at 24 hours.
perturbed_activity_alpha_48h
MPRAnalyze motif-perturbed sequence activity alpha at 48 hours.
perturbed_activity_alpha_72h
MPRAnalyze motif-perturbed sequence activity alpha at 72 hours.
functional_indicator_0h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_3h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_6h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_12h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_24h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_48h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_indicator_72h
Source per-time-point functional indicator: 1 activating, -1 dampening/repressive, 0 not significant at FDR 0.05.
functional_timepoint_count
Number of seven time points with a nonzero source functional indicator.

Quality control

The authors required at least 80% of reads for a barcode to map to one sequence and at least three supporting reads, retained barcodes represented in both DNA and RNA, and reported 9,948 of 10,041 designed sequences with usable representation. Replicate activity was highly reproducible (mean Pearson correlation 0.98 per time point). For each perturbation method, the paper required four MPRAnalyze filters: significant PERT-versus-WT activity at one or more time points, significant PERT-versus-WT temporal behavior, WT or PERT activity above SCRAM controls, and WT or PERT temporal behavior different from SCRAM (FDR < 0.05). The consensus FRS set additionally required all four filters in method 3 and either method 1 or 2 with a consistent direction, yielding 598 rows. Package QC retained all 598/598 source FRS rows after requiring valid motif/region identifiers, a recognized effect code, valid motif coordinates/strand, and finite WT/PERT activity and log2 effect values at all seven time points.

Curation notes

This is one integrated lentiMPRA time-course experiment rather than seven independent libraries. The assay begins with H1/WA-01 human embryonic stem cells (Cell Ontology embryonic stem cell, CL:0002322) and transitions toward neural progenitors during the sampled window; the single biosample field therefore records the starting cultured cell type and the time course is described here. The processed table intentionally focuses on the uniform single-motif consensus FRS atlas (598 rows); raw GEO matrices and supplementary Dataset 3 retain the broader library and double-perturbation interaction data. Coordinates and the FRS source sheet are hg19, and source gene lists were normalized only from comma-delimited to semicolon-delimited cells.

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