Friday, December 31, 2010

Books I read, 2010

I was able to put a decent dent in the ever-growing "to read" pile over the last year.  ALL of these are worth reading at least once, many of them would bear a second reading (esp. Borges, Murakami, Gibson, Beukes, Bolano, Tatsumi).  Zero History was read mostly on my phone, as were parts of The Wind-Up Bird Chronicle.  

MAKERS                             Cory Doctorow

The Savage Detectives         Roberto Bolano
Zoo City                               Lauren Beukes
Zero History                         William Gibson
The Wind-Up Bird Chronicle   Haruki Murakami
Marshall McLuhan                 Douglas Coupland
Labyrinths (first half)             Jorge L. Borges  
Black Blizzard                      Yoshihiro Tatsumi
A Drifting Life                       Yoshihiro Tatsumi
The Paradox of Choice          Barry Schwartz

Saturday, December 4, 2010

Early life stress enhances vulnerability to stress via activation of REST4-mediated gene transcription

Rat pups separated from their mothers:

1) Have increased depressive-like and anhedonic behaviours
2) Show an increased expression of the neuron-specific transcriptional repressor REST4 in the medial prefrontal cortex
3) Gene transfer induced REST4 overexpression in the medial prefrontal cortex increased vulnerability to stress

J Neurosci
Yamaguchi University

Sunday, November 14, 2010

S08 Clinical Information Warehouses. notes. #AMIA2010 #research Kamal/Payne-OSUMC, Weng-Columbia, Batal-Pitt

J. Kamal  Ohio State UMC data warehouse 
13+ year project
Information Warehouse - IW
IW Data Marts: Business, Clinical, Research, External
Started with financial. 
Web scorecards, dashboards, NLP, data mining.
Powerful ad hoc query tools.
Oracle BI Discoverer.
iCount - User Query tool for aggregates -- aggregate counts of patient cohorts to define patient populations for research grants; tied to standard terminology; all users have access. No IRB needed.
IW has >4K users 
Queries increasing exponentially.
Users: Administrators, managers, clinicinas researchers, finance.
50 dashboards of approx 1K indicators. Powerful visual reports.
Research portal, Investigator profile
CIO dashboard.
MRSA reporting
Antimicrobial
Restraint Orders
Falls
Diabetes mgmt
Genetic data storage and analysis
Patient tracker automates patient flow recording
Managers notified of idle processes

Data driven issue awareness
More scorecards
Physician Profiling system
De-identified IW
Hagop Mekhjian MD Chief Medical Officer
Posters 14, 41, 102, 46, 91, ... (11+ posters)
IW at OSUMC has Honest Broker status; Two protocols - internal+ external - worked with IRB and Research Office to 
make processes robustly meet the criteria for non-human subject research.

C. Weng et al. Comparing Effectiveness of Clinical Registry vs. Clinical Data Warehouse for Supporting Clinical Trial Recruitment: Case Study
Columbia University
TECOS Trial Evaluating Cardiovasc Outcomes w Sitagliptin

Diabetes Registry created in 2005, contains 5K patients, few variables A1C, urine microalb., LDL chol
vs. 
Clinical Data Warehouse
Too many false positives recruiting with Registry, PI turned to Informatics/Data Warehouse
Warehouse had 2X the # of variables of interest vs. Registry (8/12 vs. 4/12).
Temporarily Ineligible (awaiting result)
Definitely Ineligible
Potentially Eligible > recent visit, must be referred by their primary care provider.
Confirmed Eligible
Target n=60
                                 Registry        Warehouse
Potentially Eligible        2033             100   
Confirmed Eligible            29(6.6%)     31 (31%)
nonconsent rate                 S  i  m  i  l  a  r
No working days               74              59
Patients/wk                        1              2.5
Total in 3 months              14              30  

Registry lacked rich clinical data for evaluating exclusion criteria
Columbia Study site rated #3 of over 300+ sites worldwide.
Warehouse needs sophisticated query skills.
Registry has better quality for disease-specific markers.
CDW  more effective in excluding the ineligible.
Dynamically generated registries linked to CDW can lead to promising recruitment solutions,
Planning a dynamic Protocol-specific screening tool that utilizes CDW and Registry
PI Weng NLM R01 

Payne P. TRITON Project
Integrative Translational Research Information Management Platform
CLL Research Consortium
NCI funded P01 fo rCLL
n=5,000 cohort

Objectives:
Modernize legacy information system
provide tools to increase in research productivity
-data exchange
-bio-specimen mgmt
-adverse event detection
-protocol driven Decision support
-integraitve query and data aggregation
Provide community access to technologyes

Systems Design:
Open source, standards compliant
portal based approach
caTissue
caAERS
caGRID
SQL
MySQL
GWT environment "Google look and feel"
Current Project Status

billing, budgeting, trial mgmt, close-out and reporting

Model-driven design/architecture:
Real world protocols > represent as a logical model>map to standards and data sources

Some lessons:
Don't use just PIs - get research staff "on the ground".
Use Project Management methods.
Organization perception is just as important as technical functionality. 

Mining Clinical Data using Minimal Predictive Rules
Batal I. and Hauskrecht M., University of Pittsburgh
Rule Induction methods represent knowledge
Association Rules more complete than greedy algorithsm - eg. trees; generate a lot of rules
Add correlation measure - statistical test or interestingness measure (evaluates each rule individually
We should consider the nested structure of the rules.
Minimal Predictive Rule [MPR]:
predicts class significantly better than the subrules
Lossy pruning speeds the mining, at the risk of some missing MPRs.
A-MPR prunes 98% of the search space without changing AUC.
An efficient algorithm for approximate mining.

Friday, November 5, 2010

T. Kato on Epigenetics of bipolar disorder #ASHG2010 notes

Epigenetics of Bipolar disorder
T. Kato

Previous association studies:
Ferreira et al Nat Genet 2008
PBRM1 Nat Genet 2010
GAD1
GABA A R alpha 1
COX10
RELN

MZ discordance for bipolar disorder:
1. Point mustation
2. CNV
3. mosaicism
.
.
.

Methods - unbiased approach RED, RAPD, RDA, MS-RDA
Two pairs MZ twins discordant for bipolar disorder
488K CNV
MBD2B MBD3L1 conjugated beads Active Motif
Tiling arrays

Promoter wide DNA methylation analysis p<10^-4 by MAT
Bisulfite sequencing of 13 regions overlapping with CpG island to validate; refined p<10^-6 
HTTLPR DMR upstream 25,590,000(?correct location -- nocx not sure about this position) -- seen in ss genotype only
Beach 2010, van  IJzendoorn Biol Psy 2010
Philibert group 2010 SLC6A4 papers
see also poster 2527W Hiroko Sugawara

Posted via email from nocx

Wednesday, November 3, 2010

D. Mehta: Polymorphisms in FKBPS define biologically distinct subtypes of PTSD #ASHG2010 notes

Divya Mehta  et al
Polymorphisms in FKBPS define biologically distinct subtypes of PTSD: evidence from endocrine and gene expression studies

Individuals with PTSD have supersensitive GR.
FKBP5 is a cochaperone, part of a mature heteroGR complex, and regulator of the heteroGR complex.
FKBP5 SNPs interact with child abuse to predict PTSD symptoms. 
Binder et al. 2008; Yehuda group paper.

African American sample from suburban Atlanta.
218 participants with trauma history.
PSS (PTSD measure)
183 transcripts associated with trauma scores, none previously described.
Then they stratified transcript results by genotype*PTSD --significant interaction, no main effect.
32 significant interactions, transcripts previously identified, associated with PTSD symptoms X FKBP5 SNP rs 92950158.
Opposite effects of transcripts in carriers of risk and protective markers.

Complmented with a literature based - pathway mining approach. 
Use intermediate phenotypes.
use co-expression networks.

Posted via email from nocx

Nancy Cox: Are we looking in the wrong places? #ASHG2010 notes

Follow up to GWAS:
Sequence regions near most significant SNPs, sequence all local genes 

Transcriptome studies using lymphoblastoid cell lines -  PLoS Genetics 2010
SNPs with highest eQTLs are enriched for WTCCC Crohn's susceptibility loci
+other loci too. Pattern different in CAD, Hypertension, T2D.
Enrichment of locally acting eQTLs versus distantly acting eQTLs.
T2D had most dramatic enrichment in a late bin-- transcriptome studies using adipose and muscle tissue.
Most QTLs are distant regulators of gene expression.
Took top 1K SNPs in WTCCC T2D studies. Vast majority enriched for eQTLs acting distantly.
Cancer mostly local regulators.
T1D more local than distant.
Distant regulators quite often on different chromosomes.
Will different phenotypes have different architecture WRT distant vs. local regulators?
Does tissue specificitiy play a role?
Has implications for how we think about sequencing studies.

Posted via email from nocx

Mingyao Li Plenary on RNA Editing #ASHG2010

RNA-DNA differences = RDD
RDD are not traditional RNA editing or transcription infidelity
n=27 CEU
RNA sequences of B cells
DNA sequences from publicly available
Each person has 3.8K RDDs+/-1.6K
20K RDD sites in 4500 genes

Posted via email from nocx

Sunday, October 31, 2010

Just had coffee celebrating my first year of #ubuntu. Cool beans. @ubuntuka @WebDevOnLinux @planetubuntu @jonobacon

It started as an experiment.
Over the past twelve months Ubuntu it stopped being an experiment and became my modus operandi.
Was there a singular epiphany for me?  I don't think so.  It felt more like watching the sun rise a few times, with each installation.  On my notebook, I've done fresh installs of Karmic and Lucid; and the Meerkat upgrade.  My daughter has UNE on her netbook.
Many thanks to the Ubuntu community.  

Wednesday, October 20, 2010

Fewer sticks for diabetics? Microbead glucose monitoring.

Implantable Microbeads for Continuous Glucose Monitoring

http://stm.sciencemag.org/content/2/54/54ec164.short?etoc

Posted via email from nocx

Reversal of Depressed Behaviors in Mice by p11 Gene Therapy

Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens

Alexander et al. (STM, 2010) state: "These results suggest that p11 loss in rodent and human nucleus accumbens may contribute to the pathophysiology of depression. Normalization of p11 expression within this brain region with AAV-mediated gene therapy may be of therapeutic value. "

http://stm.sciencemag.org/content/2/54/54ra76.short?etoc

Posted via email from nocx

Monday, October 18, 2010

Nature Medicine: Negative regulator of MAP kinase involved in depression. MKP-1.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2219.html

MAP kinase phosphatase 1 (MKP-1) /DUSP1.
Another study that points to this pathway, from the lab of Ron Duman.
Expression study in human post-mortem MDD brain and rat and mouse models. 

Posted via email from nocx

Friday, October 15, 2010

Reboxetine Meta-Analysis Calls Into Question Veracity of All Industry-Sponsored Research

The recent meta-analysis in the British Medical Journal says Reboxetine is "ineffective and potentially harmful".  Publication bias evident.
http://www.medscape.com/viewarticle/730537

Monday, October 11, 2010

Genetics of gene expression #GOGE -- recent paper in @PLoS

Cheung et al. PLoS Biology 2010

Polymorphic cis- and trans-regulation of human gene expression

"The majority of the regulators act in trans to the target (regulated) genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past."

http://www.ncbi.nlm.nih.gov/pubmed/20856902

Posted via email from nocx

Monday, October 4, 2010

Epigenetic and inflammatory marker profiles associated with depression

Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample

Uddin et al. use bioinformatic analyses and find genome-wide methylation profiles differ between depressed individuals and controls.

http://www.ncbi.nlm.nih.gov/pubmed/20836906

Posted via email from nocx

Saturday, October 2, 2010

Allele-specific methylation in the human genome: Implications for genetic studies of complex disease

Allele-specific methylation is quantitative and heterogeneous, and increases genetic complexity of associations between loci and complex disease--

Meaburn et al. Epigenetics 2010

Posted via email from nocx

Monday, September 27, 2010

Dynamic instability of genomic methylation patterns in pluripotent stem cells #epigenetics #stemcells

Ooi and colleagues conclude:

"Error-prone maintenance methylation will introduce unpredictable phenotypic variation into clonal populations of pluripotent stem cells, and this variation is likely to be much more pronounced in cultured female cells. This epigenetic variability has obvious negative implications for the clinical applications of stem cells."

 Implications for complex phenotypes?

Posted via email from nocx

Wednesday, September 22, 2010

Tuesday, September 21, 2010

Liked: @AMIAInformatix EMR-enabled GWAS on peripheral arterial disease. Kullo et al.

JAMIA recently published a study which shows that EMR can be utilized to characterize phenocopies, phenotypic heterogeneity, and important related variables to support GWAS.  Their evidence supports the use of EMR-linked biorepositories for GWAS. 

Posted via email from nocx

In which S. Mani discusses Kasparov's experiment after losing to Deep Blue... #AI @AMIAInformatix

. . . and the relevance of Kasparov's experiment to medical informatics.

Note on Friedman's ‘fundamental theorem of biomedical informatics’

‘Their skill at manipulating and “coaching” their computers to look very deeply into positions effectively counteracted the superior chess understanding of their grandmaster opponents and the greater computational power of other participants. Weak human + machine + better process was superior to a strong computer alone and, more remarkably, superior to a strong human + machine + inferior process.’ - Kasparov

Posted via email from nocx

Monday, September 20, 2010

Heritability of childhood/adolescent depression. Cross-fostering experiment, IVF.


Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research

Rice and colleagues have used a "prenatal cross-fostering' design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences."
They have noted "Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother-offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother-offspring pairs and therefore was attributable to inherited factors."


http://www.ncbi.nlm.nih.gov/pubmed/19476689

Wednesday, September 15, 2010

Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index #epigenetics

Feinberg et al from Sci Transl Med --

"an unbiased genome-scale analysis of ~4 million CpG sites in 74 individuals with comprehensive array-based relative methylation (CHARM) analysis. We found 227 regions that showed extreme interindividual variability [variably methylated regions (VMRs)] across the genome, which are enriched for developmental genes based on Gene Ontology analysis. Furthermore, half of these VMRs were stable within individuals over an average of 11 years, and these VMRs defined a personalized epigenomic signature. Four of these VMRs showed covariation with body mass index consistently at two study visits and were located in or near genes previously implicated in regulating body weight or diabetes."

http://stm.sciencemag.org/content/2/49/49ra67.short?etoc

Posted via email from nocx

Network analysis of differential expression using machine learning approaches

Candidate gene prioritization by network analysis of differential expression using machine learning approaches

Using three of their own strategies to analyze gene expression scores versus Simple Expression Ranking, the 
authors found:

Our results showed that our four strategies could outperform this standard procedure and that the best results were obtained using the Heat Kernel Diffusion Ranking leading to an average ranking position of 8 out of 100 genes, an AUC value of 92.3% and an error reduction of 52.8% relative to the standard procedure approach which ranked the knockout gene in average at position 17 with an AUC value of 83.7%.
"
http://www.biomedcentral.com/1471-2105/11/460/abstract

Posted via email from nocx

Saturday, September 4, 2010

Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. #epigenetics

"We observed the presence of DNA demethylation activity, which was increased in FC nuclear extracts from mice treated with valproate (VPA, 2.2 mmol/kg, twice a day for 3 days). VPA not only reduces anxiety and cognitive deficits and other symptoms in bipolar disorder (BP) disorder and schizophrenia (SZ) patients but also upregulates Reln and glutamic acid decarboxylase 67 (Gad67) mRNA/protein expression by reducing the methylation of their promoters. We believe that the identification of an enzyme in brain that facilitates DNA-demethylation and an understanding of how drugs induce DNA demethylation are crucial to progress in a new line of pharmacological interventions to treat neurodevelopment, neuropsychiatric and neurodegenerative diseases."

Dong et al. Epigenetics. 2010 Nov 16;5(8). [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/20716949

Posted via email from nocx

Thursday, September 2, 2010

Epigenetic Transmission of the Impact of Early Stress Across Generations [via @thinkgenome]

After stressing postnatal mice for days 1-14 --

"chronic and unpredictable maternal separation induces depressive-like behaviors and alters the behavioral response to aversive environments in the separated animals when adult. Most of the behavioral alterations are further expressed by the offspring of males subjected to maternal separation, despite the fact that these males are reared normally. Chronic and unpredictable maternal separation also alters the profile of DNA methylation in the promoter of several candidate genes in the germline of the separated males. Comparable changes in DNA methylation are also present in the brain of the offspring and are associated with altered gene expression."

Posted via email from nocx

Friday, August 27, 2010

Boot time video with SSD.

Download now or watch on posterous
VIDEO0003.3gp (1934 KB)


11-12 seconds. Intel X 25 M. 2nd generation.

Posted via email from nocx

Wednesday, August 25, 2010

Night ride coming up.

Churning slow and even circles in the dark.

Posted via email from nocx

Recommendations for Biomarker Identification and Qualification in Clinical Proteomics

"commonly encountered shortcomings in fundamental aspects of experimental design mainly during biomarker discovery must be addressed in order to provide robust data. In this Perspective, we assert that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets; in addition, we describe a brief set of practical and feasible recommendations that we have developed for investigators to properly identify and qualify proteomic biomarkers, which could also be used as reporting requirements."

http://stm.sciencemag.org/content/2/46/46ps42.short?etoc

Posted via email from nocx

Tuesday, August 24, 2010

Monday, August 23, 2010

Tuesday, August 17, 2010

Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices. Xin et al. 2010, PLoS ONE

Using methylation sensitive SNP chip methods, 

prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA
methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such
differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were
validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal,
occipital, and temporal cortices are significantly more methylated as compared to the cerebellum."

Posted via email from nocx-ville

Thursday, August 12, 2010

Unlock @TELUS HTC Desire using Rogers SIM card: how to. APN settings. @RogersHelps @RogersBuzz

Here's what worked for me:

1. Get the IMEI code from your new phone after you charge it all the way.  You get this by entering *#06# into the dialer.


2. Get the SIM card unlock code for the HTC Desire from a reputable internet seller. They will need your IMEI. 
I used CellUnlock.net and they were very good.

3. Put your Rogers SIM card in the Telus Desire, put in the battery and restart your phone.

4. The Desire will prompt you for the 8 digit SIM unlock code when you try to use it. Enter it.
Now half of it should be working - you should have talk and text.  The top right will show how many
bars of signal you have. 

5. You will still need to get your data access point connected --

6. On the Desire, make sure Network Mode is set for WCDMA only, or GSM/WCDMA (which is the default).  
You will not get data on GSM only. [Go figure.]

7. Enter your new access point name (APN) and settings:
Name
Rogers
APN
internet.com
Username
wapuser1
Password
wap
MCC
302 (should already be filled in)
MNC
either 720 or 72 depending on your SIM card (should already be filled in)

Leave all other settings blank.   

http://thekidd.ca/blog/2009/05/rogers-apn-configuration-for-android-phones/

8. Save your new access point name.

9. Try playing with the browser, search or Market.  You should see the up and down arrows in the top right corner and now have data too.

 

Posted via email from nocx-ville

Wednesday, August 11, 2010

Advanced Search of the Electronic Medical Record: Augmenting Safety and Efficiency in Radiology

5 minute podcast here: 

"The design principles for the proposed
system included (1) the ability to facilitate nearly instan-
taneous, time-of-service queries of a patient’s entire med-
ical record, on the basis of a clinician’s clinical inference
(eg, “I wonder if condition X is mentioned in this pa-
tient’s record”); (2) the ability to store complex, struc-
tured queries and activate these automatically on the
basis of clinical service schedule or care unit census; (3)
the ability to rapidly filter a patient’s entire EMR data set
to a topic-specified or situation-specified dossier (subset);
and (4) the ability to transmit the output of search either
to readable forms (Web browser) or other software (ma-
chine-to-machine integration).
The result of these efforts is a system dubbed QPID
(Queriable Patient Inference Dossier), now in use daily
in our department."

Zallis and Harris, J Am Coll Radiol 2010

Posted via email from nocx-ville

Tuesday, August 10, 2010

Peripheral BDNF Produces Antidepressant-Like Effects in Cellular and Behavioral Models

Results from the Duman lab.  Will be interesting if replicated.

"Peripheral BDNF administration increased mobility in the FST, attenuated the effects of CUS on sucrose consumption, decreased latency in the NIH test, and increased time spent in the open arms of an EPM. Moreover, adult hippocampal neurogenesis was increased after chronic, peripheral BDNF administration. We also found that BDNF levels as well as expression of pCREB and pERK were elevated in the hippocampus of adult mice receiving peripheral BDNF. "

Posted via email from nocx-ville

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD via #FeedSquares

Sunday, August 8, 2010

Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Turner et al.

Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more.

Biochem Pharmacol

"the multiple first exons represent only a first layer of complexity orchestrated probably by tissue-specific transcription factors. Modulation of alternative first exon activity by epigenetic methylation of their promoters represents a second layer of complexity at least partially controlled by perinatal programming. The alternative promoter usage also appears to affect the 3' splicing generating the different GR coding variants, GRalpha, GRbeta, and GR-P."

Posted via email from nocx-ville

Thursday, August 5, 2010

Polymorphic CpG sites can be considered metastable epialleles, are thought to be particularly vulnerable to environmental influences

Dolinoy et al. 2007:

Polymorphic CpG sites can be considered metastable epialleles that are variably expressed and are thought to be particularly vulnerable to environmental influences.

http://www.ncbi.nlm.nih.gov/pubmed/17413847

Posted via email from nocx-ville

Tuesday, August 3, 2010

Shi et al. The Pharmacogenomics Journal- Genomic signatures show that classification algorithms choose phenotype-related genes

Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes

by Shi and colleagues:

"A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power."

Posted via email from nocx-ville

Monday, August 2, 2010

Arch Gen Psychiatry: CACNA1C allele associated with hippocampal and subgenual ACC dysfunction

This was an fMRI study in 110 healthy subjects:

"healthy carriers of the CACNA1C risk variant exhibit a pronounced reduction of bilateral hippocampal activation during episodic memory recall and diminished functional coupling between left and right hippocampal regions. Furthermore, risk allele carriers exhibit activation deficits of the subgenual anterior cingulate cortex, a region repeatedly associated with affective disorders and the mediation of adaptive stress-related responses."

This SNP was originally associated with Bipolar Disorder, by GWAS.

Posted via email from nocx-ville

Thursday, July 29, 2010

D'Avolio et al. JAMIA on NLP for clinical information retrieval - Evaluation of a generalizable approach to clinical information retrieval using the automated retrieval console (ARC).


Evaluation of a generalizable approach to clinical information retrieval using the automated retrieval console (ARC).

D'Avolio et al. 2010

"The ARC  . . . is available as open-source software at http://research.maveric.org/mig/arc.html "

http://www.ncbi.nlm.nih.gov/pubmed/20595303

Posted via email from nocx-ville

Monday, June 28, 2010

Tissue specific DNA methylation of CpG islands in normal human adult somatic tissues distinguishes neural from non-neural tissues.

"These data demonstrate consistent tissue specific methylation for certain CpG islands, with clear differences between white and grey matter of the brain."

Posted via email from nocx-ville

Childhood Adversity, Brain-Derived Neurotrophic Factor val/met and Serotonin Transporter Promoter Polymorphism in Adolescent Depression

NO Interaction Between Childhood Adversity, Brain-Derived Neurotrophic Factor val/met and Serotonin Transporter Promoter Polymorphism on Depression: The TRAILS Study

http://www.ncbi.nlm.nih.gov/pubmed/20553751

Posted via email from nocx-ville

Friday, June 25, 2010

Jaco Pastorius, Portrait of Tracy. 2:36 with scrolling score.

PLoS one: Plasma Protein Biomarkers for Depression and Schizophrenia by Multi Analyte Profiling of Case-Control Collections

"Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia."

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009166

Posted via email from nocx-ville

Wednesday, June 23, 2010

Learning about neuGRID

neuGRID is a user-friendly grid-based e-Infrastructure which enables the neuroscience community to collect and archive large amounts of imaging data and to access resources for computationally intensive data analyses.

Posted via email from the nocx files

Nat Nanotech: Carbon nanotube eletrodes

High-power lithium batteries from functionalized carbon-nanotube electrodes

http://www.nature.com/nnano/journal/vaop/ncurrent/abs/nnano.2010.116.html

Posted via email from the nocx files

Sunday, June 20, 2010

Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels

"Using a global, comparative CpG methylation profiling approach we identified many novel examples of active DNA demethylation and characterised accompanying transcriptional and epigenetic events at these sites during monocytic differentiation. We show that active DNA demethylation is not restricted to proximal promoters and that the time-course of demethylation varies for individual CpGs."

http://genomebiology.com/2010/11/6/R63/abstract

Posted via email from the nocx files

Thursday, June 10, 2010

Canada, Check Your Privacy Settings [notes] #ncwk

Canada, Check Your Privacy Settings
Ann Cavoukian IPC
Ronald Deibert
Mod Jesse Hirsh

Ann Cavoukian
Need to get rid of zero sum game notion: functionality verus privacy is a bad news game.
Privacy relates to personally identifiable identifiers (PII) name address, social insrance number
Open access – re public information, non-PII.
Fundamental essence is that user controls PII. User in control. For non-PII, there should be little if any control.
Privacy=Freedom
State censorship the antithesis of privacy.
Human condition thrives on freedom.
Informational Self-Determination. Individual determines the fate of their information. Germany a world leader.
Privacy does not equal security.
Can have strong security without privacy.
You must have both.
Privacy is the first to go out the window e.g. 9/11.
We need to change the paradigm.
Need to prevent harms. Must prevent data breaches.
Change paradigm from zero-sum to positive sum, win-win.
Privacy must be embedded into the design of a system.
Add-on does not work as well as intrinsic methods.
End-to-end lifecycle protection – data destruction.
Respect for individuals.

Deibert
Tracking Ghostnet
Shadows in the Cloud

Victims of cyber espionage dozens of governments media, UN, Deloitte, Associated Press
Advanced social engineering using email – Well written, real details malicious attachments /payload
One of the computers compromised was an antivirus service in Taiwan.

Indian govt compromised – 700 documents recovered that had been stolen. e.g. Armed Forces. Defense contract information.

Ghostnet and Shadows a disturbing arms race in cyberspace.
Disturbing geopolitical competition. Domain that is carved up, colonized and militarized.
Needed:



  1. Global Treaty of Cyberspace needed. Because the web is a valuable commons.


  2. Global Monitoring and Early Warning System International Information sharing Mechanisms.


  3. Support Cyberspace Openness

Discussion
European Privacy leadership and FTC and FCC leaders are embracing privacy by design.
Younger generations value privacy as much as older.
R. Deibert discusses ethical and legal framework of University and Canada. Citizenlab workers risk being declared spies by other countries.
Anything you put out, be mindful -- it could end up anywhere, without control.
Cloud computing/social network data does exist on real servers which may exist in jurisdictions where privacy legislation is different than here.
Many parts of the world there is no oversight, e.g. anonymous web surfing service hands over data to a research lab's request.
Smartgrid – will have privacy-by-design embedded in its development.

R. Deibert laments metamorphsois of word hacking. Hacking was originally about tinkering, not lawlessness. #hacktivism Now we have a litigious culture of fear. e.g. Don't open this digital lock, have a lawyer with you when you read your EULA.

Question re emerging models of Electronic Health Records. Cavoukian Answer – Ontario is tied for last, at the bottom, with Nunavut, for EHR use. Cavoukian wants EHRs with privacy, the positive sum game. Says this as a patient who has had procedures. Cavoukian contacted Telus re HealthSpace, wanted to test it.

Q: The power government and capital have in benefiting from a lack of privacy.
A. Cavoukian and others influenced Google to make default gmail account secure.
Biometric encryption – there is no representation of your actual biometric – in Netherlands and Israel.

Cavoukian to @cavoukian: “Have the guts to put your own name on it . . . Appalling.”

The Future of the Web and the World [notes] #ncwk

The Future of the Web and the World

Gerri Sinclair

Lucy Bernholz

John Thackara

Mod Jesse Brown


Gerri Sinclair on the Future, trends.

Moore's Law + Network effect > change amplified

Trends:

  1. Recombinant innovation – knowledge recombined, mashed up

  2. Beyond eLearning – lectures and slides uploaded, Open University. New models of collaboration – wikis. e.g. www.khanacademy.org

  3. Demise of the professional - growth of the professional amateur

  4. Openness ubiquitious - Open Source; Open Data

  5. Mathematician as rockstar breakthrough in mathematics, data deluge; consumer as data.

  6. Transparency vs. privacy. Loss of privacy, but new accountability. Wikileaks- US Army. Classified data leaked in searchable format.

  7. Threats/ benefits of the cloud. Gmail, Facebook,

  8. Big Brother is watching you. Japan/Korea. Wireless sensors+robotics

  9. Evolution of the Web - 3d immersification

  10. Gameification of media – Education, Health, Fitness. Digital media becoming fundamental currency of eduction. Game engines, tourism, health, environment.

  11. Reality continuum – hybrid reality (SMS/homework); AR; continuous partial attention; Book Exodus to the Virtual World

  12. Online Demographics. Silent Gen. /Boomers/Gen X/ Gen Y/ Gen V (Avatars- relationships will be primarily digital). Penguin Club. Cartoon Doll Emporium.

  13. Multiple identities – Who am I?


Lucy Bernholz:

Technology having effects on how people do good.

Most ideas from her talk found in paper – Disrupting Philanthropy.

Data will be platform for change.

e.g. Action supporting Haiti earthquake relief by cell phone or computer. #crisiscamp

> went global – Ottawa London Bogata; no institutional support. Peoplefinder app for tagged photos of missing relatives. Creole > English tweet translator.

“Data is anything that can be digitized.”

Grandma biggest fan of iPad.

Phone gives proximity to data and expertise, gives value to organizations.

Fundamental upset to the role of the institution.

Governance is a problem for groups like Crisis Commons. Not an official nonprofit.

Laws will need to change.

A revolution in where social goods come from and how they change.

New roles for public, private, independent sector.

“We have a very new meaning of place.”

New defintions of scale – can be small and global at the same time.


John Thackara:

I don't want to be led by technology. It's a means for us to do things.

What needs to be fixed and how do we do it?

Doomsday economy: Actions described as positive for economy, direct consequences for

biosphere. Pretty serious.

Alternative solidarity economy: In some places, people are reorganizing their daily lives for reduced impact on environment.

The hours spent looking after others are ways of creating social good, just not yet described yet as economic activity. A very European point of view. More people have access to mobile phones than clean water in the world. Depraved: replacing care by people with care by machines.

You can't grow food with an iPhone.

You shouldn't look after an elderly person with an iPhone.

Brown/Bernholz interlude: OLPC > tablets, netbooks, drove price of tech down.

myc4.org >> micropayments to Africa – you control over investment vs. loan, set your own interest rate.


Panel – a sharing economy will be a huge part of sustainability

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Wednesday, June 9, 2010

The collapse of gene complement following whole genome duplication

Prediction of CpG-island function: CpG clustering vs. sliding-window methods

Hackenberg et al. show that their clustering method, CpGcluster, is better at detecting short, often differentially methylated CpG islands
than sliding-window methods.
"The major difference in the prediction was found for short islands (CpG islets), often exclusively predicted by CpGcluster."

http://www.biomedcentral.com/1471-2164/11/327/abstract

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Monday, June 7, 2010

Learning about tools that use gene #ontology for analysis of gene expression and #microarray data #GO

Big bundle of tools here, many web-based.
Make sure to read the disclaimer at the top of the page:

http://www.geneontology.org/GO.tools.microarray.shtml

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Cell Research: SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm and epistasis in bipolar disorder

Hu et al.

SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm, efficiently reveals the risk of genetic epistasis in bipolar disorder.

Hu and colleagues developed a method for analyzing epistasis in a GWAS of complex traits, and exclude the contamination of marginal effects caused by single-locus association. They analyzed the Wellcome Trust Case Control Consortium's (WTCCC) bipolar disorder GWAS data.

http://www.nature.com/cr/journal/vaop/ncurrent/full/cr201068a.html

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Sunday, May 30, 2010

Pharmacogenomics: Is miRNA the future of phenotyping?

MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine.

You can get the paper here

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Monday, May 24, 2010

Extensive sequence-influenced DNA methylation polymorphism in the human genome

Hellman and Chess: Methylation is not independent of SNPs.

http://www.epigeneticsandchromatin.com/content/3/1/11

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GREAT improves functional interpretation of cis-regulatory regions, via @thinkgenome

'Genomic Regions Enrichment of Annotations Tool' 
Mclean et al. 
Nat Biotechnol 28:495–501 2010

The software completes an analysis showing which genes a transcription factor is likely to influence, and the relevant molecular pathways, across the genome.  It incorporates proximal and distal binding and controls for false positives using a binomial test.

http://www.nature.com/nbt/journal/v28/n5/abs/nbt.1630.html

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Wednesday, May 19, 2010

Anonymization of electronic medical records for validating genome-wide association studies

The "approach automatically extracts potentially linkable clinical features and modifies them in a way that they can no longer be used to link a genomic sequence to a small number of patients, while preserving the associations between genomic sequences and specific sets of clinical features corresponding to GWAS-related diseases."

http://www.pnas.org/content/early/2010/04/05/0911686107.abstract

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Tuesday, May 11, 2010

Genome Medicine: Locus Reference Genomic sequences: an improved basis for describing human DNA variants.

The Locus Reference Genomic (LRG) sequence format "builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-file record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants."

http://genomemedicine.com/content/2/4/24/abstract

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Sunday, May 9, 2010

BMC Genomics: Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood

"We conclude that about 904 miRNAs are expressed in human leukocytes."

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Current Opinion Neurobiol: MicroRNA pathways in neural development and plasticity, in press

Methylation Linear Discriminant Analysis (MLDA) for identifying differentially methylated CpG islands

"This approach utilizes linear regression models of non-normalised hybridisation data to define methylation status. Log-transformed signal intensities of unmethylated controls on the microarray are used as a reference. The signal intensities of DNA samples digested with methylation sensitive restriction enzymes and mock digested are then transformed to the likelihood of a locus being methylated using this reference. We tested the ability of MLDA to identify loci differentially methylated as analysed by DMH between cisplatin sensitive and resistant ovarian cancer cell lines. MLDA identified 115 differentially methylated loci and 23 out of 26 of these loci have been independently validated by Methylation Specific PCR and/or bisulphite pyrosequencing."

http://www.biomedcentral.com/1471-2105/9/337

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Cgaln: fast and space-efficient whole-genome alignment

"Cgaln takes less than 13 hours to finish an alignment between the whole genomes of human and mouse in a single run on a conventional desktop computer with a single CPU and 2 GB memory."

http://www.biomedcentral.com/1471-2105/11/224

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Friday, May 7, 2010

NEJM Effect of Bar-Code Technology on the Safety of Medication Administration via @dirkstanley

"Observers noted 776 nontiming errors in medication administration on units that did not use the bar-code eMAR (an 11.5% error rate) versus 495 such errors on units that did use it (a 6.8% error rate)" P<0.001

http://content.nejm.org/cgi/content/short/362/18/1698

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Thursday, May 6, 2010

Analysis of a polymorphic microRNA target site in the purinergic receptor P2RX7 gene

Science: A Draft Sequence of the Neandertal Genome

"a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world"

http://www.sciencemag.org/cgi/content/full/328/5979/710

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PNAS: Epigenetic and immune function profiles associated with posttraumatic stress disorder

n=23 cases 
77 controls
"immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD."

Could this be a result of HPA axis dysregulation?

http://www.pnas.org/content/early/2010/04/19/0910794107

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The case for cloud computing in genome informatics

"impending collapse of the genome informatics ecosystem"

http://genomebiology.com/2010/11/5/207

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Sunday, May 2, 2010

BMC Medical Genetics - Characterizing the founder structure of the Old Order Amish. via @BioMedCentral.

128 founders (78 females and 50 males) accounted for over 95% of the mean relative founder contribution among living Old Order Amish descendants, according to analyses with PedHunter 2.0.

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McLuhan on the objectives of new media.

"The objectives of new media have tended, fatally, to be set in terms of the parameters and frames of the older media."

-Marshall McLuhan

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@huffingtonpost: Electronic Medical Record Shift: Signs Of Harm Emerge As Doctors Move From Paper

Machines don't make things perfect. Some of the known issues with
computers in health care are discussed, including electronic ordering.

http://www.huffingtonpost.com/2010/04/20/electronic-medical-record_n_545441.html

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Sunday, April 25, 2010

The state of speech recognition in GNU/Linux.

ViaVoice for GNU/Linux was pulled by IBM.
Current/future possiblities might include simon and CMU Sphinx.

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@doctorow's law applied to DRM; a benevolent dictatorship. #iPad

"If someone takes something that belongs to you, and puts a lock on it that you don't have a key for, that lock isn't in your best interests."
"Anytime someone puts a lock on something you own, against your wishes, and doesn't give you the key, they're not doing it for your benefit."
-Cory Doctorow

In his recent Publisher's Weekly article, Cory reviews why "Already, Apple's App Store has displayed the warning signs of a less-than-benevolent dictator."

______________________________________________________________________________________________________________________

http://www.eff.org/deeplinks/2009/04/doctorows-law

http://www.theimaginationage.net/2009/02/doctorows-law.html

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