Long noncoding RNA main paper

Welcome to the FANTOM5 long noncoding RNA (lncRNA) main paper page. This page will be used to list tasks and discuss ongoing analyses for the paper. For information on ncRNA data resources, see the Noncoding RNA central page. Please keep in mind that this paper has already been the subject of extensive discussion in many forums and we need to move quickly on this paper. While we are always interested in exciting new analyses, if you have something new to introduce/propose please do so with the intention of personally carrying out the analysis.

Paper objectives, leadership, and communication

This paper aims to capture, and functionally define, the complete breadth and diversity of the non-redundant set of long noncoding RNA (lncRNA) genes in the human genome, while leveraging the unique qualities of FANTOM5 (hCAGE, RNAseq, >1k human cell and tissue samples) to fully characterize the cell type specificity, timecourse responsiveness, regulatory network participation, and evolutionary impact of these genes. For the purpose of this paper, it is important to note that our definition of lncRNAs is broader than that used by others, and includes, in addition to lincRNAs (long intergenic ncRNAs), all bidirectional/nested/cis-antisense lncRNAs and unspliced single-exon lncRNA genes with hCAGE, RNAseq, and/or pre-F5 cDNA/EST support. In addition, this paper will use genome organization and context coupled with hCAGE-measured expression of coding genes to probe functional properties and provide a comprehensive classification scheme for lncRNAs.

Paper coordinators:

1. Max Burroughs, Nicolas Bertin - main OSC coordinators and contacts (burrough@gsc.riken.jp and nbertin@gsc.riken.jp)
2. Leonard Lipovich - senior coordinator (llipovich@med.wayne.edu)
3. Al / Piero / WP4 / WP6 - overall supervision and co-direction; procurement and organization of datasets and validations.

Communication: We will have specific lncRNA main paper TeleConference calls, currently beginning after the main F5 call finishes.

Outline of the paper, including key tasks and their assignments

If you are interested in assisting with a task below, please add your name before the task in parantheses. Names have already been added for people expressing interest or currently involved in tasks as discussed at the FANTOM5 Koyo meeting. There are still tasks with no one assigned, if you are interested please put your name down. Conceivably, some of these tasks will end up as satellite papers which will be referred to by the main paper but we are including them here at present.

Annotation/analysis of the non-redundant lncRNAome across FANTOM5 dataset

Leonard Lipovich's lab has undertaken and completed the Herculean task of assembling and annotating the set of non-redundant, known lncRNAs and supplemented this with the set provided by Gencode. We already updated the non-redundant gene-centric human lncRNA catalog ("the F5 lncRNAome") with RNAs from Cabili et al Genes & Dev 2011. Preliminary viewing of the analysis in ZENBU suggests many lncRNAs are tissue-specific; this is an important point of order for the FANTOM5 data and this main paper.

Specific tasks:

1. (Leonard, Hui) Generation of the definitive gene-centric non-redundant FANTOM5 lncRNAome: "the" human lncRNA catalog (XLS, BED)
   1. (Leonard, Hui) Inclusion of latest lncRNAs from the Cabili et al and the Gencode lncRNA Derrien et al papers - done, links at line above
   2. (Leonard, Hui) FUNDAMENTAL CHARACTERIZATION OF THE LNCRNAOME, identifying and counting lncRNAs in each of the following categories:
      1. standalone spliced lncRNA (consistent with "lincRNA" definition)
      2. standalone single-exon lncRNA
      3. lncRNA in a gene pair
         1. bidirectionally promoted lncRNA
         2. lncRNA nested intronically inside another gene, in the same direction as that gene
         3. sense-antisense lncRNA
            1. exonic antisense overlap with another gene
            2. intronic antisense overlap with another gene
   3. (Max, Leonard, OSC) increasing the non-redundant lncRNAome by incorporating novel transcripts identified through FANTOM5 hCAGE and RNA-seq data - still To Do
2. (WP4, Nicolas, Max, Kawaji-san, Leonard, Al) IN PROGRESS: generation of the transcript-centric (but gene-anchored) lncRNAome that will incorporate all transcripts of all lncRNA genes from across all of our lncRNAome data subsets. This is a significant upgrade to our current gene-centric (one usually arbitrarily selected transcript per gene) lncRNAome. 11 DEC 2011
3. (WP4, Nicolas, Leonard) Obtain the list of hCAGE promoter peaks from UPDATE012 and UPDATE013 associating with lncRNAome from the final filtered and normalized clustering values (Question: Where is the final list of Clusters that we should use for this? - LL)
4. (Lukasz, and Tom Freeman!) Primary-cell specific expression
   1. (Lukasz) Top-expressed lncRNAs in the total dataset and (Tom Freeman?) in different tissues (made available on the wiki to sample providers)
   2. (Tom Freeman) Identification of "cell-type" specific lncRNAs (made available on the wiki to sample providers)
5. (Lukasz, Win Hide, and Emmanuel Dimont!) Time course expression (IMPORTANT NOTE: THIS SUBSECTION MAY NEED TO MOVE FROM THE LNCRNA MAIN PAPER TO THE TIMECOURSE MAIN PAPER, DUE TO F5 TIMECOURSE DATA RELEASE CONSTRANTS.)
   1. (Lukasz) Significant differences in lncRNA expression across time points across all time courses
   2. (Lukasz) lncRNA expression shared across multiple time courses
   3. (Win, Emmanuel) lncRNAs that go from low to high (or from high to low) in any specific timecourse
   4. (Win, Emmanuel) complete SwitchEngine analysis of lncRNA expression in timecourses
6. (Lukasz) Analysis of lncRNAs (done in comparison with analysis of coding RNA--i.e. main promoterome paper analysis)
   1. (Lukasz) House-keeping vs tissue-specific lncRNAs (vs. coding RNAs)
   2. (Lukasz) Clustering of primary cells/tissues with respect to their lncRNA expression profiles (Question: Lukasz, how is this different from Tom F's stuff? - LL)
   3. (Lukasz) PCA and multidimensional scaling to find tissues with most lncRNA expression differences / similarity (vs. coding RNA)
7. (Lukasz) All of the above tasks can be repeated to look for differences in cis- and trans-acting lncRNAs (see below)
8. (how about Vlad or Boris J here?) tissue-specific differential promoter usage in lncRNAs; comparison to coding differential promoter usage

General functional classification of lncRNAs

Here we define the subset of lncRNAs likely to be acting in "cis" based on their genomic proximity to their putative cis-target or co-regulated genes, and develop specific, network-level functional predictions for individual lncRNAs based on co-expression. We also attempt to identify all lncRNAs involved in "trans" regulation (i.e. regulation of genes that reside outside of the lncRNA-encoding locus), and lncRNAs which may function as precursors for small/er RNA biogenesis. While there is some overlap in the analyses, due to the fact that some RNAs are probably involved in more than one of these three functional modalities, they are treated in separate sections below.

cis-acting lncRNAs

Specific tasks:

1. (Nicolas, Leonard) Preliminary classification of cis-acting lncRNAs
   1. (Nicolas) calculating (PCC) and ranking sense-antisense co-expression at all ~ 2,800 manually annotated lncRNA-mRNA sense-antisense ("SAS") pairs (from the 4,511-pair F5 SASome provided by Leonard) in latest data updates (012 and 013)
   2. (Leonard) annotation of the above into a curated set representing top-ranking co-regulated and anti-regulated lncRNA-mRNA SASpairs; emphasis on pairs containing mRNAs that encode transcriptional regulators (will use DAVID, Panther to ID them)
   3. (Leonard) update of the FANTOM3 human "Chainome" (already obtained from Engstrom et al) to hg19; identification of all lncRNA-containing chains; addition of new lncRNA-containing chains from non-Engstrom sources (Emily) to update the F5 Chainome
2. cis-acting lncRNA analysis (each analysis performed on both the lncRNA-containing SASome extracted by Nicolas and the lncRNA-containing chainome curated by Leonard's lab)
   1. (Timo, Robin, Nicolas) linking lncRNA expression to groups of locally-connected genes (QUESTION: What is "locally-connected?" Are you referring to genomic neighbors here, but to in-trans co-expression or ontology-based connections when this outline item re-appears in the section below on trans-acting lncRNAs? - LL)
   2. (Eivind, Finn, Tom, Nicolas) co-expression analysis to inform function of individual lncRNAs and effects of lncRNAs on chains including both co-expressed gene ontology and cell tree ontology (i.e. co-expression of mRNAs in-cis, and/or of specific ontological categories of mRNAs in-trans, across related cell lineages gives clue to function)
      1. co-expression patterns to search for include lncRNA chains where all members are expressed; and chains where lncRNA is expressed and mRNA is not, and vice/versa.
   3. (Michiel) MARA analysis to see influence of cis-acting lncRNAs on transcriptional network (see motif enrichment section below)
   4. (Eivind, Helena, Max) overlaying small RNA information with ncRNA found in chains (QUESTION: What is this? Is it redundant with stuff elsewhere in the outline? - LL)
      1. similar to above, search for potential effects on expression of chains in presence/absence of small RNA and its orientation
      2. (Eivind, Helena, Max, Martin, Asai-sensei / CBRC (see structure section below)) lncRNAs serving as possible small RNA precursors, and identification of novel structures in long RNAs

trans-acting lncRNAs

1. (all) identification of potential trans-acting lncRNAs and their classes (classes: general trans-acting, Alu-element acting, and short RNA precursor transcripts)
   1. (Timo, Robin, Nicolas) linking lncRNA expression to groups of locally-connected genes
   2. (Eivind, Finn, Tom, Nicolas) co-expression analysis to inform function of individual lncRNAs including both co-expressed gene ontology and cell tree ontology (i.e. co-expression across related cell lineages gives clue to function)
   3. (Eivind, Helena, Max, Martin, CRBC (see structure section below)) ncRNA serving as possible small RNA precursors
   4. (Nicolas) reverse, window-based homology analysis of trans-acting lncRNAs to determine potential sites of activity on the genome
      1. overlay this analysis with co-expression results
   5. (Yulia) direct/inverse co-expression patterns of lncRNAs with known-gene mRNAs with Alu elements in 3'UTRs (based on Gong and Maquat 2011 Nature paper)
      1. (Hui, Leonard may assist w/ this) requires construction of the set of mRNAs with Alu elements in the 3' UTR to specifically look at effects of expression in these lncRNAs/potential target mRNAs
   6. (Sarah D.) identification of all lncRNAs that are cis-antisense to pseudogenes and that therefore may regulate in-trans the parental genes of the pseudogenes (check recent papers by Kevin Morris, this is a very "hot" area that we must cover)

RNA processing of the F5 lncRNAome: empirical evidence from hCAGE/RNAseq/CAGEscan integration

1. RNA processing at exonic sense-antisense overlaps of lncRNA-mRNA pairs
   1. Cleavage and 5' capping of putative 3' cleavage fragments that map to SAS overlaps: capped (hCAGE and CAGEscan) data
      1. (Leonard) Case study: BDNF/BDNFOS (asymmetric capped cleavage products, symmetric uncapped short RNAs from SAS overlap)
      2. (?) Global analysis: Which of our ~ 2,800 annotated SAS overlaps give rise to capped? uncapped? symmetric? asymmetric? both?
2. RNA processing of lncRNAs that serve as hosts of functional short RNAs
   1. Cleavage and 5' capping of 3' cleavage fragments located within the host lncRNA and after the mature short RNA sequence
      1. (Leonard) Case study: AK044422
3. Human-mouse non-conservation of RNA processing: orthologous mouse loci that do not recapitulate the human pattern of capping and polarity (e.g. Bdnf); orthologous human loci that do not recapitulate the mouse pattern of cleave-and-cap after miRNA sequences (AK044422)

Identification of novel lncRNAs using RNA-seq/CAGE-scan

see RNA-seq page for details.

1. (Max) collection of usable public RNA-seq data
2. (Max) integration with FANTOM5 RNA-seq
3. (Nicolas, Max) CAGE-scan integration
   1. (Nicolas) Use CAGE-scan to look specifically for lncRNA TSSs inside repeats
   2. (Nicolas, Max) tabulation of all novel lncRNAs from this data and incorporation into non-redundant lncRNAome
4. (Leonard, Hui) nonredundant incorporation of the combined data into the F5 lncRNAome: Go To Annotation/analysis of the non-redundant lncRNAome across FANTOM5 dataset, task 1, subtask 3
5. (Laurens) annotation of a set of novel lncRNAs (Question: Which set? Can Laurens annotate the novel RNAseq/CAGEscan hits, or was the original plan to rely on the HAVANA annotation of other F5 lncRNAome entries that was presented at the Koyo Meeting? - LL)

Motif enrichment in promoter regions of lncRNAs

1. (Boris Jankovic) Motif enrichment and lncRNA-specific regulatory programs
   1. Comparison 1: lncRNA promoters vs protein-coding-gene promoters (reported at Koyo Meeting)
   2. Comparison 2: promoters of cis-acting vs trans-acting lncRNAs (To Do)
2. Location/orientation of binding motifs within promoters
3. (Michiel) MARA analysis on lncRNAome to identify possible candidates important to the transcriptional network

lncRNA conservation in matching mouse primary cells

Anayzing the presence/absence of lncRNA peaks in mouse VS human for samples available in both species. Because lncRNAs are less conserved than protein-coding genes, it is possible that lncRNAs play a specific role in shaping the human/primate transcriptome. Many of these analyses could also be extended to aortic smooth muscle cells in rat, dog, and chicken. There are three specific kinds of conservation that we are interested in analyzing: i) sequence (using UCSC TransMap and liftOver), ii) gene structure (location and presence/absence in the genome of lncRNAs; including chain conservation), iii) expression.

Specific tasks:

1. (?) mapping human lncRNAs to mouse (TransMap/liftOver)
   1. (?) sequence conservation (-500/+500 TSS promoter regions vs. exons of full-length transcripts)
      1. (?) frequency
      2. (?) relative cis- vs. trans- conservation
      3. (?) promoter regions vs. full-length of transcripts
   2. (?) conservation of gene structure between the lncRNA genome location in human and the orthologous locus in mouse
      1. (?) presence/absence of lncRNAs (e.g. present in human, absent in mouse; but nearby known genes are conserved)
      2. (?) Positional Equivalents (Engstrom et al 2006 FANTOM3 definition)
         1. (?) genomewide discovery of tag-only Positional Equivalents (human: cDNA/EST and hCAGE support; mouse: hCAGE-only support)
      3. (?) relative cis- vs. trans- conservation (QUESTION: How will we approach this? - LL)
      4. (?) conservation and partial conservation of the chainome
   3. (?) expression conservation
      1. (?) performed for conserved matches identified in 1.1 and also for conserved chains identified in 1.2
2. (Yulia for global analysis, Leonard for annotation) frequency OF REPEAT-initiated TSS in lncRNA in humans vs. mouse (QUESTION: Do we have, or need, RNAseq/CAGEscan data from mouse for this? - LL)

Network validation

Probing lncRNA function through perturbation in identified networks.

Specific tasks:

1. (Emily, Leonard) selection of candidate target cis-networks involving transcription of transcription factor or epigenetic modifier genes that are antisense to lncRNAs (in pairs or chains)
2. (Max? Harukazu? WP6?) Which of these loci already have lncRNA-mRNA cis-co-expression (of a pair or of at least some part of a chain) in any of the cell line systems that are available for validation? What cell lines can we choose from?
3. (coordinated by Harukazu, WP6) knockdown of lncRNAs, measuring local influence of lncRNAs to identify candidates for genome-wide perturbation experiments
   1. (WP6) probing transcriptional network perturbations through knockdown CAGE-seq
4. (WP6) look into feasibility of overexpression experiments
   1. (Matthias Harbers) provide RIKEN / KK DNAFORM Clone IDs matching the lncRNAs that we may want to overexpress

Structure features/subclassification of lncRNAs

The intention here is to provide a classification of lncRNAs based on structural features (including computational secondary structure prediction and overlap with other genomic features) with the help of RNA-seq and short RNA data (e.g. splicing architecture, evidence of processed intermediates, translational potential, recapping, positioning relative to other genome markers, etc.)

1. (Eivind, Max, Helen) overlap with short RNA (TSS-based and other processing products), see short RNA page
2. (?) overlap with other genome features
3. (?) RNA-seq and splicing frequency
4. (Hui Jia, Ben Brown) translational potential (small reading frames; overlap all exonic lncRNA sequences from the combined F5 lncRNAome -vs- public ENCODE proteogenomic data, and list all lncRNAs that are either mis-classified mRNAs or have evidence of ectopic translation)
5. (CBRC) secondary structure of lncRNAs (NOTE: As only a small proportion of lncRNAs appear to be conserved, we are wondering what could be done to limit the influence of conservation on the secondary structure calculations. - LL, Max)
   1. small-RNA-like (pre-miRNA? piRNA-like? others?) structures (hairpins) and known-ncRNA like (tRNA-like?) structures (stems/loops) in all F5 cDNA/EST, RNAseq, and CAGEscan lncRNA sequences
      1. overlap of these predicted structures, if any, with known (UCSC sno/miRNA, tRNA etc tracks) small RNAs
   2. prediction of novel secondary structures specific to the long RNAs, including but not limited to pseudoknots; identification of novel structural lncRNAs that do not function by processing into shorter RNAs
   3. structure differences that correlate with our different lncRNA classifications (cis- vs trans-, chain vs. non-chain, convergent vs divergent structure in SASpairs, spliced lncRNAs vs. single-exon lncRNAs, known-shortRNA-containing vs non-containing, etc.)

eRNA analysis

eRNA (enhancer RNA) is a class of lncRNA of particular interest, transcribed from enhancers (which act cryptically as lncRNA promoters) and involved in spatial and epigenetic cis-regulation of nearby and distant target genes. Analysis of eRNA is being headed up by Robin Andersson (robin@binf.ku.dk).

(BASIC QUESTION: Since eRNAs are polyA-, how do we look for them in F5 data? Which F5 datasets - hCAGE, RNAseq, CAGEscan, some subsets or all of these - retain polyA- transcripts? - LL)

Specific tasks:

1. (Robin) identification/classification, percent lncRNAs that are eRNAs, along with rationale
2. basic statistics (e.g. length distribution, etc.) (HOW DO WE KNOW THIS FROM F5 DATA WHICH IS INHERENTLY NOT FULL-LENGTH? - LL, I think length distribution will also be dependent on overlap with RNA-seq, other statistics could include length between eRNA and nearest promoter, etc. - Max)
3. cell specificity
4. exploring relationship between eRNA and associated promoters interactions
   1. expression correlation
   2. mutual information approach
   3. intersection with publicly available spatial genomic organization data
5. (Miura-san, Robin, Nicolas) validation of eRNA interaction with promoter regions by intersect with existing HiC (?) data and/or more targeted validations
6. (Leonard) curation of polyA+ cDNA/EST data suggesting polyA+ lncRNA transcription from loci that also give rise to polyA- eRNAs (e.g. EVF-2 locus DLX5/6 enhancer, and its paralogous locus DLX1/2 enhancer, clearly give rise to polyA+ lncRNAs in cDNA/EST data)

lncRNA and human disease overlap

1. (Kenny, Peter, Juha) overlaying GWAS data with lncRNA
   1. cis-/trans-enrichment, cell-specificity of affected lncRNAs, etc...
   2. How about specific identification of F5 lncRNAs in disease regions where no causative genes have yet been identified, and using these RNAs' expression profiles from F5 to make the case for their relevance to the particular disease/s? - LL
2. (Leonard, Alka) Rett Syndrome and cis-chains
   1. clinical and translational relevance of the F5 lncRNAome: putative antisense eRNAs in a Rett region precisely recapitulate the exact brain expression profile of a leading Rett candidate gene
   2. Alka: inclusion of any info on patient deletions of this region depends on approval from and inclusion of your clinical collaborators - LL

miRNA promoters: Please move this to Satellite page, or explain how it fits into the main paper :-)

Satellite paper based on Eivind and Kawaji-san's work

1. (Eivind/Kawaji-san) definition of miRNA promoters based on DROSHA-KD, small RNA-seq and upstream hCAGE peaks

Timeline/order of analyses (Who-does-what and when; we will fold this into the outline above, as this is currently redundant)

Instead of wasting time assigning a bunch of meaningless dates to each task, I'll work out some of the dependencies which gives an idea of the prioritization. Then we'll follow up with groups assigned to the tasks as soon as they can be accomplished. The lists below are structured to imply dependency (indented tasks follow non-indented tasks...)

This is all dependent on finalization and normalization of the Kawaji-san promoterome clusters; however, everything listed below can begin using available data. After RNA-seq is used to confirm novel lncRNAs from FANTOM5, we may need to rerun a selected portion of the analyses on this set and possibly on the integrated set.

Network validation

Given the time this will require, we should get moving with what we have currently.

• Small-scale (starting immediately):
  • Current best targets from Emily and Leonard sent to the OSC (Max and Al) (done, 4 chains).
  • Al and Max list of available experimental systems to Leonard (done for the 4 chains)
    • Leonard--> ZENBU curation of co-expression at these 4 loci in the available experimental systems (cell lines).
    • Max and Al--> discussion with WP6.
• Genome-wide (ongoing effort to get more cis-networks for validation):
  • Hui/Leonard to update Par Engstrom's FANTOM3 chainome to hg19 - done!
  • Nicolas to infer TF gene - lncRNA gene co-expression at TF-lncRNA SASpairs inside all updated FANTOM3 chains (To Do)
  • Nicolas/Leonard to have ongoing pipeline of new chains to be validated by Al / WP6

Annotation/analysis of the non-redundant lncRNAome across FANTOM5 dataset

• Leonard submits final tweaks to the lncRNAome (all done)
  • Lukasz perform listed tasks (can begin ASAP; a "beta" run, do not wait for RNAseq)
    • listed tasks are performed again on classified cis-acting and trans-acting lncRNAs, looking for differences
• novel lncRNAs (from F5 RNAseq mapping to Al's new unique CAGE peaks) are added to the set
  • potentially repeat above analyses a 3rd time (on all including F5-RNAseq-only lncRNAs)

General functional classification of lncRNAs

• Nicolas cis-acting classification (can begin now, don't wait for RNAseq; use F5 SASome and hg19-updated chainome)
  • Leonard annotation of selected co-expressed lnc-mRNA cis-pairs, beginning with, but not limited to, TF-lncRNA pairs
    • Timo, Robin, Nicolas establishing locally-connected genes with lncRNA chains
    • Eivind, Finn, Tom, Nicolas co-expression analysis on chains and complete set
  • Leonard / Hui: basic identification of F5 lncRNAs that do, and don't, overlap any known small RNAs (miRNAs, snoRNAs, piwiRNAs)
    • identification of all lncRNAs that lack the potential to function as host of any known small RNAs
    • Eivind, Helena, Max overlaying small RNA information on chains and effects of small RNA on expression
• Eivind, Finn, Tom, Nicolas co-expression analysis on trans-acting lncRNAs
• Nicolas identifying complete space of physical interaction for trans-acting lncRNAs
  • Nicolas overlaying the above two; re-do analysis (mid 2012 before submission) with new F5 RNAseq lncRNAs
• construction of the Alu element-containing mRNA list
  • Yulia Alu elements role in trans-acting lncRNA gene-targeted expression

Motif enrichment in promoter regions of lncRNAs (can begin now from 20k lncRNAome, don't wait for RNAseq)

• Boris J. motif enrichment
• Michiel MARA

Analysis of lncRNA promoters using ENCODE data

• Finn : File:LncRNA regulation Rye Drablos 23-11-2011.pdf

lncRNA conservation in matching mouse primary cells

• Al matched human/mouse samples
• Leonard assists in defining determinants of lncRNA conservation
  • list of mouse/human sequence conserved sites
  • ? sequence conservation
  • ? genome structure conservation (includes chains)
    • expression conservation human/mouse based on conserved pairs identified in above two points
  • ? basic statistics on human/mouse conservation (possibly dependent on cis-/trans- classification)
• ? compilation of conservation statistics (e.g. frequency, etc...)

Identification of novel lncRNAs using RNA-seq/CAGE-scan

see RNA-seq page.

• Laurens will receive the complete set of novel lncRNAs for further annotation

Structure features/subclassification of lncRNAs

• Eivind Max Helen overlap with short RNA see short RNA page
• CBRC general structural features of identified classes of lncRNAs
• take list of lncRNAs with overlapping short RNAs from above
  • CBRC identification of "precursor" structure from RNA-seq and short RNA
  • CBRC secondary structure predictions of lncRNAs in short RNA regions
    • CBRC integration of the two above
  • CBRC identification of novel and nonconserved lncRNA structures (incl pseudoknots?) that do not depend on short RNA?

eRNA analysis

• Robin percentage of lncRNAs that are eRNAs and rationale for choosing this
• Robin basic statistics/cell specificity
• Robin eRNA and affected promoter analysis
  • Robin/others computational validation with public datasets
• Miura-san wet lab validation
• Leonard/Hui overlap of polyA- eRNAs with polyA+ lncRNAs; catalog of loci that give rise to both

lncRNA and human disease overlap

• global: Kenny/others GWAS overlap with lncRNAome set
  • accompanying analysis
• example: Leonard and Alka pursue Rett story
  • potential eRNA and/or cis-regulatory lncRNA in FOXG1 region (partially done, presented at Koyo)