Integrated lentiMPRA of human–chimpanzee neural CRE orthologs
Differentially Active and Conserved Neural Enhancers Define Two Forms of Adaptive Noncoding Evolution in HumansA lentiviral MPRA tested 2,274 designed pairs of human and chimpanzee orthologous cis-regulatory elements in induced-pluripotent-stem-cell-derived neural progenitor cells and neurons. The packaged table contains the 179 published CREs with differential activity across the authors' combined 12 biological assays, joined to tested human GRCh38 coordinates and supplemental annotations.
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
The library used 171-bp CRE oligos with six unique 11-bp barcodes per enhancer, an 18-bp ClaI/SalI spacer, a minimal promoter, an EGFP reporter, and barcodes in the EGFP 3'-UTR. The lentiviral library was delivered at MOI 10 to species-matched iPSC-derived neural progenitor cells and neurons from three human iPSC lines (H20961, H28126, H28815) and three chimpanzee lines (C3649, C4955, C8861), with three biological replicates per species and cell type; RNA/DNA barcode amplicons were sequenced by NextSeq 2x150 bp 48 h after infection. Target organisms are Homo sapiens (NCBITaxon:9606) and Pan troglodytes (NCBITaxon:9598); biosamples comprise iPSC-derived neural progenitor cells and neurons, so no single organism or biosample CURIE is appropriate for this aggregate experiment.
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 · 21 definitions
- cre_id
- Study CRE identifier (CRE.1–CRE.2274).
- chromosome
- Human GRCh38 chromosome from Supplementary Table 7.
- start_hg38
- 0-based inclusive human GRCh38 BED start coordinate from Supplementary Table 7.
- end_hg38
- 0-based exclusive human GRCh38 BED end coordinate from Supplementary Table 7.
- length_bp
- CRE interval length in base pairs, end_hg38 - start_hg38.
- library_class
- Library design class: Accelerated CRE for CRE.1–CRE.1579 or Brain CRE for CRE.1580–CRE.2274.
- reported_limma_logfc
- Published Supplementary Table 8 limma logFC for the species contrast, reported without sign alteration.
- human_minus_chimp_log2fc
- Derived negative of reported_limma_logfc; positive values indicate higher inferred human-ortholog activity.
- average_log2_activity
- Published limma AveExpr for the CRE species contrast.
- limma_t_statistic
- Published limma moderated t-statistic.
- p_value
- Published limma p-value.
- fdr
- Published adjusted p-value from Supplementary Table 8.
- b_statistic
- Published limma B-statistic (log-odds of differential expression).
- selection_p_value
- Published positive-selection p-value from Supplementary Table 9 when the CRE was in that set.
- selection_annotation
- Published selection set annotation (accel or brain) from Supplementary Table 9.
- nearest_gene_ids
- Semicolon-separated gene symbols associated with the CRE in Supplementary Table 2 CRE-Gene.
- nearest_ensembl_ids
- Semicolon-separated Ensembl gene IDs corresponding to nearest_gene_ids.
- nearest_gene_distances_bp
- Semicolon-separated distances from CRE to the associated gene TSS in bp, as reported in Supplementary Table 2; blank values preserve missing source entries.
- wnt_pathway_genes
- Semicolon-separated Wnt-pathway genes associated with the CRE in Supplementary Table 3, if any.
- neuropsychiatric_snp_ids
- Semicolon-separated neuropsychiatric GWAS SNP IDs in the CRE-SNP window table (Supplementary Table 2), if any.
- qc_pass
- TRUE for all retained rows; these are the 179 published differential-activity CREs that passed the authors' active-element/replicate filtering.
Quality control
The authors' library QC found approximately 91% of designed oligos present in the pCRE library and approximately 72% of designed oligos with at least one perfect match; pMPRA QC recovered 12,777 unique oligos, approximately 77% of the designed library. For assay reads, paired reads were merged with NGmerge; barcodes were counted only when the barcode and three flanking bases on each side exactly matched the design and every barcode base had Q >= 14. RNA reads were retained only when the same oligo had DNA reads in the same replicate; RNA and DNA counts were CPM-normalized and expressed as RNA/DNA ratios. Of 2,274 designed orthologous CRE pairs, 1,157 were tested; CREs required expression in at least two replicates of either species/cell type, yielding about 268 active CREs for differential analysis. Limma across 12 biological replicates identified the published 179 differential-activity CREs. This package retains those 179 published result rows; no additional count-based filter was applied because the public submission lacks the separate barcode-to-CRE assignment library needed to recalculate element-level counts from the SRA reads.
Curation notes
This is one aggregate experiment because Supplementary Table 8 reports differential activity across all 12 biological assays; the public run metadata describe DNA and cDNA libraries for three human and three chimpanzee lines in neural progenitor-cell and neuron conditions, but no cell-type-specific activity matrix was deposited. Supplementary Table 8 does not explicitly label the limma contrast orientation. The CRE.2170 example near FZD1 is described in the paper as having higher human activity, while its reported logFC is negative, indicating that the reported value is likely chimpanzee-minus-human; human_minus_chimp_log2fc therefore reverses the sign. This orientation is an inference. The table is a clean re-expression of the published differential-activity CRE results joined to author-supplied coordinates and annotations, not a reconstruction from raw reads. The source table contains all 179 author-reported differential-activity rows, including ten with adjusted p-values above 0.05; they were not re-filtered by statistical significance because the package preserves the reported result set. The separate barcode-to-CRE lookup needed for element-level reassignment is not publicly included in the SRA submission; the SRA/ENA metadata and original supplementary archive are preserved in raw_data.