LRT in bioinformatics papers

Take a look at the the LRT and empirical P-value calculation in following examples:

Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1) - Nature Genetics: "Thus, gene-dropping is done under the null hypothesis of linkage equilibrium and no linkage. To calculate an empirical P value, gene-dropping is carried out multiple times. Here, at least 50,000 simulations were carried out for each analysis. The likelihood ratio test statistic (LRT) from each gene-dropping iteration is compared to the LRT for the observed data. The empirical P value is the proportion of iterations in which the gene-dropping LRT equaled or exceeded the observed LRT. In general, the obtained empirical P values of gene-dropping are more conservative than asymptotic P values for small sample sizes."

http://www.smd.qmul.ac.uk/statgen/dcurtis/lc/gctests.html
The asymptotic p value is 0.00027, as reported in the output from scanassoc. The empirical p value is calculated as (r+1)/(N+1), where N is the number of permutations performed and r is the number of permuted datasets which by chance produce a higher for the LRT statistic than does the real dataset. In order to test whether the p value was really as low as 0.00027 one would want to do 9999 or more permutations. In fact, rungc incorporates a feature called "sequential Monte Carlo testing". This means that a target can be set for the number of permuted datasets to reach the value produced by the real dataset and if this target is reached then the simulation procedure can be terminated early.

Improved detection and annotation of transposable elements in sequenced genomes using multiple reference sequence sets.

Just a test~

Combining Flock (for blog post and RSS reader) and Connotea, you can get notice for the latest added reference and write blog after reading it, which is very COOL!!

copy

Improved detection and annotation of transposable elements in sequenced genomes using multiple reference sequence sets.

Nicolas Buisine, Hadi Quesneville, and Vincent Colot

Genomics 91 (5), 467-75 (May 2008)

info:pmid/18343092 | info:doi/10.1016/j.ygeno.2008.01.005

Posted by pareng to transposable elements on Tue Apr 22 2008 at 13:48 UTC | info | related

View Original Article

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MiRNA learning note (1)

MicroRNA-143 and -145 in colon cancer. [DNA Cell Biol. 2007]
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs (20-22 nucleotides) that negatively regulate gene expression at the translational level by base pairing to the 3' untranslated region of target messenger RNAs.
"It is predicted that 30% of protein-encoding genes are regulated by miRNAs."

Principles of microRNA regulation of a human cellular signaling network : Article : Molecular Systems Biology: "By analyzing the interactions between miRNAs and a human cellular signaling network, we found that miRNAs predominantly target positive regulatory motifs, highly connected scaffolds and most downstream network components such as signaling transcription factors, but less frequently target negative regulatory motifs, common components of basic cellular machines and most upstream network components such as ligands."

Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos -- Yu et al. 35 (1): 152 -- Nucle: "We found that the expression levels of miRNA targets are lower in all mouse and Drosophila tissues than in the embryos. We also found miRNAs more preferentially target ubiquitously expressed genes than tissue-specifically expressed genes. These results support the current suggestion that miRNAs are likely to be largely involved in embryo development and maintaining of tissue identity."

NB: This kind of expression survey at different ontogenetic stages is very important, because it covers a blind spot in analyses that depend on functional categories. For example GO analyses include categories for "development", but as Yu and colleagues point out, many genes change in expression during development that are not part of the "developmental" categories. (from John Hawks's weblog)

Identification of specific sequence motifs in the ...[Comput Biol Chem. 2007] - PubMed Result: "The significantly reduced frequency of occurrence of all 20 motifs in the regions 2000 bp upstream of 23,570 human RefSeq genes demonstrated that these motifs were specific to the upstream miRNA sequences. The most frequently observed motif M1 (GTGCTTMTAGTGCAG), with a MEME E-value of 3.8e-57 was distributed within 500 bp upstream of stem-loop sequences and was also miRNA-specific."

Regulatory circuit of human microRNA biogenesis. [PLoS Comput Biol. 2007] - PubMed Result: "Newly identified regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The motifs are highly enriched in G and C nucleotides, in comparison with the nucleotide composition of miRNA upstream sequences. Although the motifs were predicted using sequences that are upstream of miRNAs, we find that 99% of the top-predicted motifs preferentially occur within the first 500 nucleotides upstream of the transcription start sites of protein-coding genes; the observed preference in location underscores the validity and importance of the motifs identified in this study. Our study also raises the possibility that a considerable number of well-characterized, disease-associated transcription factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression in diseases such as cancer."

"Further analysis of predicted miRNA-protein interactions lead us to hypothesize that TFs that include c-Myb, NF-Y, Sp-1, MTF-1, and AP-2alpha are master-regulators of miRNA expression."

Spatial regulation of microRNA gene expression in the Drosophila embryo: "we investigate the possibility that localized expression is mediated by tissue-specific enhancers, comparable to those seen for protein-coding genes."

mir-309–6 polycistron (8-miR) : An 800-bp 5′ enhancer was identified that recapitulates this complex pattern when attached to a RNA polymerase II core promoter fused to a lacZ-reporter gene.

mir-1 gene: a mesoderm-specific enhancer located ≈5 kb 5′ of the miR-1 transcription unit.

Evidence is presented that the 8-miR enhancer is regulated by the localized Huckebein repressor, whereas miR-1 is activated by Dorsal and Twist. These results provide evidence that restricted activities of the 8-miR and miR-1 miRNAs are mediated by classical tissue-specific enhancers.

Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila -- Casillas et al. 24 (10): 2222 -- Molecular Biology and Evolution

Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila -- Casillas et al. 24 (10): 2222 -- Molecular Biology and Evolution: "We find that point mutations in intronic and intergenic CNSs exhibit a significant reduction in levels of divergence relative to levels of polymorphism, as well as a significant excess of rare derived alleles, compared with either the nonconserved spacer regions between CNSs or with 4-fold silent sites in coding regions"

TOADD: more about the methods.

//Long time, no reading~

assembly error or additional rearrangement?

1. Rearrangement Rate following the Whole-Genome Duplication in Teleosts -- Sémon and Wolfe 24 (3): 860 -- Molecular Biology and Evolution: "Rearrangement Rate following the Whole-Genome Duplication in Teleosts"

check out to see whether there is higher RR in zebrafish, theoretically.

2. ScienceDirect - Genomics : Phylogenetic analysis of three complete gap junction gene families reveals lineage-specific duplications and highly supported gene classes: "Note that in one of the zebrafish clusters the orientation of the two genes is inverted (cx41.8, cx44.1), suggesting an additional chromosomal rearrangement on the zebrafish chromosome."



3. Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis -- McEwen et al. 16 (4): 451 -- Genome Research: "In only two cases were all dCNE family members found to be located in the introns of paralogous genes (NBEA and LRBA) that were not the likely target genes. In these two specific cases the predicted target genes, MAB21L1 and MAB21L2, are also located in introns of NBEA and LRBA, respectively."

very interesting and important case! New paper in PLoS One, "Ancient Origin of the New Developmental Superfamily DANGER" also mentioned the Mab21L1/2. Check out!

papers about fish evolution

1. The Evolutionary Fate and Consequences of Duplicate Genes, Science 10 November 2000:
http://www.sciencemag.org/cgi/content/full/290/5494/1151

2. Genome evolution and biodiversity in teleost fish, Heredity (2005) 94, 280–294.
http://www.nature.com/hdy/journal/v94/n3/full/6800635a.html

a review from J-N Volff

3. Functional Divergence of Two Zebrafish Midkine Growth Factors Following Fish-Specific Gene Duplication, Genome Res. 13:1067-1081, 2003
http://www.genome.org/cgi/content/full/13/6a/1067

Instance about "mdka and mdkb underwent functional divergence after duplication".

4. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications, BMC Genomics 2007, 8:312
http://www.biomedcentral.com/1471-2164/8/312

new paper from Axel Meyer's group. Could be kind of explanation to GRB evolution.

new papers summary

New papers to read from the last week

1. Non-coding RNAs in Ciona intestinalis.
Bioinformatics. 2005 Sep 1;21 Suppl 2:ii77-8.
PMID: 16204130 [PubMed - in process]

2. Into the heart of darkness: large-scale clustering of human non-coding DNA.
Gill Bejerano1, David Haussler and Mathieu Blanchette
Bioinformatics. 2004 Aug 4;20 Suppl 1:i40-8.
PMID: 15262779 [PubMed - in process]

* I don't know why myNCBI sent me this paper until now. It's a paper in 2004. My Godsh~ But, it's def a good paper, which is obvious from the author list.

3. Exploiting conserved structure for faster annotation of non-coding RNAs without loss of accuracy.
Bioinformatics. 2004 Aug 4;20 Suppl 1:i334-41.
PMID: 15262817 [PubMed - in process]

4.Regulation of the Gene Encoding GPR40, a Fatty Acid Receptor Expressed Selectively in Pancreatic Cells.
JBC
could be a story about subfunctionality by tissue/cell.

5. Ultraconserved non-coding sequence element controls a subset of spatiotemporal GLI3 expression.
Dev Growth Differ. 2007 Aug;49(6):543-53.
PMID: 17661744 [PubMed - in process]

6. Dissecting the action of an evolutionary conserved non-coding region on renin promoter activity.
Nucleic Acids Res. 2007 Jul 26; [Epub ahead of print]
PMID: 17660193 [PubMed - as supplied by publisher]