Archive for the 'critsum0mg' Category

« Older posts
Newer posts »

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes – Genome Res.

December 27, 2013

Long-span PET mapping reveals characteristic patterns of #SVs in… cancer [v norm] genomes, but no MEIs or small events
http://genome.cshlp.org/content/early/2011/04/05/gr.113555.110.abstract

The described study used long paired-end-tags (PET) to analyze and compare SVs in cancer and normal genomes. It determined the prevalence of different types of SVs in normal and cancer sample. Overall, the results are interesting and convincing on a qualitative level; however, for the reasons outlined below, more precise and quantitative delineation of the observed effects is highly desirable.

1) Small sample size of normal genomes (only 2 normal genomes)

2) Validation rate was low (< 77%) for everything except deletions, and for singletons it was even lower. .

3) Long PET is not good for finding smaller events (few kbps). Thus, this analysis missed smaller scale SVs and cancer rearrangements.

4) While there is a discussion about breakpoints and associated repeats, it is not very informative as breakpoint locations were not determined to basepair resolution.

5) No MEI were considered — particularly, no cancer MEI were considered in the analysis, while recently it was found that somatic retrotransposition occurs in cancer (Lee et al., PMID: 22745252)..

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes –

Hillmer AM, Yao F, Inaki K, Lee WH, Ariyaratne PN, Teo AS, Woo XY, Zhang Z, Zhao H, Ukil L, Chen JP, Zhu F, So JB, Salto-Tellez M, Poh WT, Zawack KF, Nagarajan N, Gao S, Li G, Kumar V, Lim HP, Sia YY, Chan CS, Leong ST, Neo SC, Choi PS, Thoreau H, Tan PB, Shahab A, Ruan X, Bergh J, Hall P, Cacheux-Rataboul V, Wei CL, Yeoh KG, Sung WK, Bourque G, Liu ET, Ruan Y.

Genome Res. 2011 May;21(5):665-75. doi: 10.1101/gr.113555.110. Epub 2011 Apr 5.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , , , , , ,

Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions

December 6, 2013

Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions
L Ward & M Kellis
http://www.sciencemag.org/content/337/6102/1675.abs

In general we know that conservation across species and within humans are correlated. In this paper the authors focus on emphasize the exceptions to this trend. They show that although only ~5% of the human genome is conserved across mammals, regulatory regions in an additional 4% of the genomes are conserved amongst humans. They also show that some elements are conserved across mammals but lack functional activity from ENCODE data and also do not show purifying selection amongst humans. The authors pinpoint regulatory regions near color vision and nerve-growth genes for that show human-specific constraint. This has been criticized in various publications since there are other genes that are higher up in the authors’ list but harder to explain for lineage-specific constraint.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , ,

Epigenomic alterations in localized and advanced prostate cancer – Neoplasia

November 27, 2013

Summary for:

“Epigenomic Alterations in Localized and Advanced Prostate Cancer” Lin PC, Giannopoulou E, Park K, Mosquera JM, Sboner A, Tewari AK, Garraway LA, Beltran H, Rubin MA*, Elemento O*. 2013. Epigenomic alterations in localized and advanced prostate cancer. Neoplasia

http://www.ncbi.nlm.nih.gov/pubmed/23555183

In this paper, the authors take advantage of new advances in reduced representation bisulfite sequencing, a method for measuring DNA methylation patterns genome-wide, with high coverage and
single-nucleotide resolution, to study methylation patterns in prostate cancer. Working with a prostate cancer cohort already studied with DNA-Seq and RNA-Seq analyses, the authors identified
differentially methylated regions (DMRs), comparing the methylation of prostate cancer samples to benign prostate samples. The analysis found an increase in DNA methylation in prostate cancer samples, and that the methylation was more diverse and heterogeneous compared to the patterns of benign samples. Furthermore, it was found that genes near hypermethylated DMRs tended to have decreased expression, while genes near hypomethylated DMRs tended to have increased expression. Additional analyses revealed that breakpoints associated with prostate-cancer-specific deletions, duplications, and translocations tended to be highly methylated in benign prostate tissue. Finally, a study of CpG islands at different stages of prostate cancer (benign vs. PCa vs. CRPC (castration-resistant prostate cancer)) revealed that certain islands become increasingly methylated with disease severity. The authors used this data as the basis for two classification models: one to discriminate between benign prostate tissue and PCa tissue, and another to discriminate between PCa tissue and CRPC tissue. Both models demonstrated high sensitivity and specificity, indicating that CpG islands with high discriminatory power could serve as a diagnostic basis for predicting disease aggressiveness. Finally, additional analyses revealed that breakpoints associated with
prostate-cancer-specific deletions, duplications, and translocations tended to be highly methylated in benign prostate tissue.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , , , ,

HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants

November 27, 2013

http://nar.oxfordjournals.org/content/40/D1/D930.long

HaploReg explores functional annotations, such as chromatin states in varied cell types, sequence conservation, regulatory motif
alterations and eQTLs, of linked SNPs or indels within LD block of queried SNPs. The output provides a the guide to develop hypotheses of functional impact of non-coding variants, especially GWAS SNPs. HaploReg is currently limited to known variants (e.g. 1000 Genome variants and dbSNPs) and is unable to deal with private variants.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , ,

Whole-genome reconstruction and mutational signatures in gastric cancer – Genome Biol.

October 12, 2013

Genome Biol. 2012 Dec 13;13(12):R115.

Whole-genome reconstruction and mutational signatures in gastric cancer. Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PE, Teo AS, Cutcutache I, Zhang Z, Lee WH, Sia YY, Gao S, Ariyaratne PN, Ho A, Woo XY, Veeravali L, Ong CK, Deng N, Desai KV, Khor CC, Hibberd ML, Shahab A, Rao J, Wu M, Teh M, Zhu F, Chin SY, Pang B, So JB, Bourque G, Soong R, Sung WK, Tean Teh B, Rozen S, Ruan X, Yeoh KG, Tan PB, Ruan Y.

http://www.ncbi.nlm.nih.gov/pubmed/23237666

Some thoughts, much from WC:

Looks like the data is freely available via GEO ID : GSE30833 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30833

The article by Nagarajan et al. highlights the authors efforts to utilize de novo genome assembly of gastric cancer genomes to detect not only single nucleotide variants (SNV’s) and short
insertions/deletions (indels), but also larger scale genomic structural variation (SV) that could be signatures of cancer genomes. It is to be applauded that this is a whole genome analysis.

The authors present several interesting findings such as enrichment for C->A and T->A mutations in both cancer genomes, enrichment for C->A and C->T mutations in the H. pylori infected cancer genome (evidence of cytosine specific transcription mediated DNA repair due to deamination), and amplification and deletion of regions on chromosome 12 in the non-H. pylori infected genome.

Although copy number variants (CNV) could potentially be detected by exome sequencing alone, whole genome sequence enables the precise localization of such events, as well as the detection of variation in non-coding regions.

Their methodology relies on combining high-throughput short-read sequencing with longer DNA-PET (paired end tags) in order to construct higher confidence de novo assemblies with longer contiguous regions.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , ,

Thoughts on Network deconvolution as a general method to distinguish direct dependencies in networks

September 29, 2013

The opposite of clique completion: #Network deconvolution.. to distinguish direct dependencies http://go.nature.com/dVzNwC via @taziovanni

Network deconvolution as a general method to distinguish direct dependencies in networks

Soheil Feizi, Daniel Marbach, Muriel Médard & Manolis Kellis

http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2635.html

My thoughts:

Indirect relationships in a network can confound the inference of true direct relationships in a network. T, so this paper sought to develop a quantitative framework, termed network deconvolution (ND), to infer direct relationships and remove false positives in a network by quantifying and then removing indirect transitive relationship effects. The mathematical framework assumes that (1) an indirect relationship (edge) can be approximated as the product of its component direct edges and that (2) the observed edge weights are the sum of the direct and indirect edge weights – a linear dependency. The main application seems to be in mutual information (MI) and
correlation-based (COR) networks. They applied ND to various scenarios such as local network connectivity prediction (FFL
prediction), gene regulatory network prediction (in E. coli), prediction of interacting amino acids in protein structures (MI network) and coauthorship relationship network and found that (1) it can be used with various networks beyond just MI and COR (2) it can be used alone or more powerfully in combination with existing
methods/algorithms to improve predictions. In a sense it is the opposite of clique and module completion approaches (such as k-core).

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , ,

Exploring the human genome with functional maps.

November 11, 2012

This paper has: (1) Large-scale datasets compiled from literature and databases, (2) comprehensive gold standards for positive and negative samples, (3) a classifier algorithm (regularized Bayesian), and (4) further analysis beyond “functional prediction”, including an interaction network. It predicts a list of genes having some possible functions, and the authors have experimentally validated them.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694471/

Genome Res. 2009 Jun;19(6):1093-106. Epub 2009 Feb 26.
Exploring the human genome with functional maps.
Huttenhower C, Haley EM, Hibbs MA, Dumeaux V, Barrett DR, Coller HA, Troyanskaya OG.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: ,

Tissue-specific functional networks for prioritizing phenotype and disease genes.

November 8, 2012

Large-scale genomic datasets can easily be transformed into various networks. The authors aimed to infer for each particular edge, whether or not it shows up in a particular tissue by training a model based on well curated tissue-specific expression as gold standards. The algorithm arrives at different tissue-specific networks from large-scale genomics datasets; without surprise, tissue-specific networks are more informative in predicting genes corresponding to diseases related to that particular tissue. For instance, a
testis-specific network performs better in predicting genes associated with male fertility phenotypes.

http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002694 PLoS Comput Biol. 2012 Sep;8(9):e1002694.
doi: 10.1371/journal.pcbi.1002694. Epub 2012 Sep 27.
Tissue-specific functional networks for prioritizing phenotype and disease genes.
Guan Y, Gorenshteyn D, Burmeister M, Wong AK, Schimenti JC, Handel MA, Bult CJ, Hibbs MA, Troyanskaya O

Posted in critsum0mg, SciLit | Leave a Comment »
Tags:

Aneuploidy prediction and tumor classification with heterogeneous hidden conditional random fields.

November 5, 2012

This paper introduces a new method for detecting copy number variants in cancer genomes that addresses deficiencies of previous detection methods. The new method, dubbed HHCRF by the authors, adds the use of sequential correlations in selecting classification features for inferring copy numbers and identifying clinically relevant genes. This improvement results in higher accuracy on noisy data, and the identification of more clinically relevant genes, relative to previous methods. These results were obtained by testing HHCRF on both simulated array-CGH microarray data, and on actual breast cancer, uveal melanoma, and bladder tumor datasets.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677736/
Bioinformatics. 2009 May 15;25(10):1307-13. Epub 2008 Dec 3. Aneuploidy prediction and tumor classification with heterogeneous hidden conditional random fields.
Barutcuoglu Z, Airoldi EM, Dumeaux V, Schapire RE, Troyanskaya OG.

Posted in critsum0mg, SciLit | Leave a Comment »
Tags: , , ,

Ordered Cyclic Motifs Contributes to Dynamic Stability in Biological and Engineered Networks. Proceedings of the National Academy of Sciences (2008)

September 15, 2012

Summary adapted from from Koon-Kiu (KKY):

This paper studied cyclic motifs (cycles) in biological and
technological networks. A cycle can be characterized by the number of clockwise and counter-clockwise links, the number of pass-through nodes and the number of sources/sinks, etc. Direct counting of cycles of various length suggests a dependence between neighboring links, and such dependence is modeled by an interacting spin model. Fitting to the spin model shows that neighboring links tend to be in opposite directions (antiferromagnetic), resulting in a depletion of feedback loops in networks. Stability analysis concluded that the lack of feedback loop stabilizes the system in terms of perturbation around the fixed point.

Ma’ayan A, Cecchi GA, Wagner J, Rao AR, Iyengar R, Stolovitzky G. Ordered Cyclic Motifs Contributes to Dynamic Stability in Biological and Engineered Networks. Proceedings of the National Academy of Sciences 105, 19235-40 (2008) PMID: 19033453
http://ukpmc.ac.uk/abstract/MED/19033453/reload=0;jsessionid=aeku6lFJSKlT8wnr9czW.12

Posted in critsum0mg, SciLit | Leave a Comment »
Tags:

« Older posts
Newer posts »