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What genomic sequences make protein-coding genes generate divergent expression in closely related species, specifically, differentiate humans from apes, puzzle many researchers. Many studies examined species-specific gene birth, gene loss, and changes in promoters and transcription factor binding sites, but the identification and impact of human-specific lncRNAs remain unexplored. This study identified human-specific lncRNAs from GENCODE-annotated human lncRNAs, predicted their DNA binding sites (DBSs) genome-wide, and analyzed the DBSs and their counterparts in modern humans (CEU, CHB, and YRI), archaic humans (Altai Neanderthals, Denisovans, and Vindija Neanderthals), and chimpanzees. The results reveal how human-specific lncRNAs and their DBSs have transcriptionally regulated gene expression human-specifically. The rewiring of gene expression has undergone continuous evolution, significantly changed gene expression in the brain, promoted the adaptive evolution of humans, and influenced differences in modern humans. These results reveal the importance of human-specific lncRNAs (for human evolution) and highlight the importance of other species-specific lncRNAs.

Correlation between objects is prone to occur coincidentally, and exploring correlation or association in most situations does not answer scientific questions rich in causality. Causal discovery (also called causal inference) infers causal interactions between objects from observational data. Inferred causal interactions in single cells provide valuable clues for investigating molecular interaction and gene regulation, identifying critical diagnostic and therapeutic targets, and designing experimental and clinical interventions. The report of causal discovery methods and generation of single-cell data make applying causal discovery to single-cells a promising direction. However, how to evaluate and choose causal discovery methods and how to develop workflow and platform remain challenges. We report the workflow and platform CausalCell (http://www.gaemons.net/causalcell/causalDiscovery/) for performing single-cell causal discovery. The workflow/platform is developed upon benchmarking four kinds of causal discovery methods and is examined by analysing multiple scRNA-seq datasets. Our results suggest that different situations call for different methods and the constraint-based PC algorithm plus kernel-based conditional independence tests suit for most situations. Relevant issues are discussed and tips for best practices are recommended.

What genomic sequences make protein-coding genes generate divergent expression in closely related species, specifically, differentiate humans from apes, puzzle many researchers. Many studies examined species-specific gene birth, gene loss, and changes in promoters and transcription factor binding sites, but the identification and impact of human-specific lncRNAs remain unexplored. This study identified human-specific lncRNAs from GENCODE-annotated human lncRNAs, predicted their DNA binding sites (DBSs) genome-wide, and analyzed the DBSs and their counterparts in modern humans (CEU, CHB, and YRI), archaic humans (Altai Neanderthals, Denisovans, and Vindija Neanderthals), and chimpanzees. The results reveal how human-specific lncRNAs and their DBSs have transcriptionally regulated gene expression human-specifically. The rewiring of gene expression has undergone continuous evolution, significantly changed gene expression in the brain, promoted the adaptive evolution of humans, and influenced differences in modern humans. These results reveal the importance of human-specific lncRNAs (for human evolution) and highlight the importance of other species-specific lncRNAs.