Friday, May 31, 2019

Abstract for talk at the MRC LMB Cambridge

Personal Genomics & Data Science 

In this seminar, I will discuss issues in transcriptome analysis. I 
will first talk about some core aspects - how we analyze the activity 
patterns of genes in human disease. In particular, I will focus on 
disorders of the brain, which affect nearly a fifth of the world's 
population. Robust phenotype-genotype associations have been 
established for a number of brain disorders including psychiatric 
diseases (e.g., schizophrenia, bipolar disorder). However, 
understanding the molecular causes of brain disorders is still a 
challenge. To address this, the PsychENCODE consortium generated 
thousands of transcriptome (bulk and single-cell) datasets from 1,866 
individuals. Using these data, we have developed a set of 
interpretable machine learning approaches for deciphering functional 
genomic elements and linkages in the brain and psychiatric disorders. 
In particular, we deconvolved the bulk tissue expression across 
individuals using single-cell data via non-negative matrix 
factorization and found that 
differences in the proportions of cell types explain >85% of the 
cross-population variation. Additionally, we developed an 
interpretable deep-learning model embedding the physical regulatory 
network to predict phenotype from genotype. Our model uses a 
conditional Deep Boltzmann Machine architecture and introduces lateral 
connectivity at the visible layer to embed the biological structure 
learned from the regulatory network and QTL linkages. Our model 
improves disease prediction (by 6-fold compared to additive polygenic 
risk scores), highlights key genes for disorders, and allows 
imputation of missing transcriptome information from genotype data 
alone. In the second half of the talk, I will look at the "data 
exhaust" from transcriptome analysis - that is, how one can find 
additional things from this data than what is necessarily intended. 
First, I will focus on genomic privacy: How looking at the 
quantifications of expression levels can potentially reveal something 
about the subjects studied, and how one can take steps to protect 
patient anonymity. Next, I will look at how the social activity of 
researchers generating transcriptome datasets in itself creates 
revealing patterns in the scientific literature. 



Abstract for talk at the UNIVERSITY OF BERN


My talk will focus on how to leverage thousands of functional genomics datasets to deeply annotate the disease genome and perform data mining to discover disease-associated regulators and variations.


First, I will introduce our computational efforts to perform large-scale integration to accurately define distal and proximal regulatory elements (MatchedFilter) and then show how our extended gene annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend.


Second, I will look at our comprehensive regulatory networks of both transcription factors and RNA-binding proteins (TFs and RBPs). I will showcase their value by highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of the well-known oncogenic TF MYC.


Third, I will introduce a workflow to prioritize key elements and variants. I will showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS (LARVA, MOAT & uORF tools). Targeted validations of the prioritized regulators, elements and variants demonstrate the value of our annotation resource.


Finally, I will put all these methods together through application to kidney and prostate cancers.



Friday, May 17, 2019

Business Proposal

Premier Oil Plc,      
23 Lower Belgrave Street SW1W 0NR,
Attention: Account/Finance manager
Hello, My name is Zachary Edward Noah, Account/Finance manager in (Premier Oil PLC).
I have a business proposal that will be beneficial to you and me.
please contact me for more details of the business to you. thanks.
Forward your response to this email:

Saturday, May 11, 2019



A Japanese Company is currently seeking individual businesses or business expatriate to represent and act as an intermediary to her customers within Canada and US exclusively.

Best regards,
Zhang Min-hong.

Friday, May 3, 2019

Business Proposal

Premier Oil Plc,      
23 Lower Belgrave Street SW1W 0NR,
Attention: The President/CEO
Business Proposal
Having consulted the bank here in United Kingdom and based on the information I got about you on the database of your country, I have the privilege to
request your partnership and assistance on the transfer the sum of Ј10,500,000.00 (Ten Million, Five Hundred Thousand Great British Pounds) into your bank
accounts within a couple of weeks.
The above sum resulted from a contract payment made into the corporate account of a foreign contractor that carried and completed a particular contract with
my company (Premier Oil PLC) Five Years ago. With the demise of the director few months after the payment in a Gas explosion the management of the bank
has expected the relative or business associates of this late contractor to put in claims on this fund without success, with the ongoing Brexit negotiation,  the
management of the bank has just sent an official letter to the management of my company (Premier Oil PLC) to provide the next of kin or business associate of
this late contractor within 14 bank working days or the fund be declared un claimable in accordance with the laws here in United Kingdom.
I am contacting you to stand as my foreign partner and trustee to enable me present you before the management of my company as the business associate of
this late contractor. It is important to inform you that as a staff of this company that this payment originated, I cannot claim this fund without the collaboration of
a foreign trustee, hence I have contacted.
The proceed should split between us 50% of the total sum is for me and 45% for you as my foreign trustee and partner 5% for local and international incidental
expenses in the course of actualizing this fund transfer into your nominated bank account.
In the execution of this project that is of mutual benefit to all, I will request you to forward to me the following details:-
(1)    Your Name in full.
(2)    Your contact Address in Full
(3)    Your direct Mobile/cell phone number.
(4)    Brief information on your profile, age and nature of work.
Be rest assured that this transaction is 100% risk free and whatever information should be restricted between us until this fund transfer into your nominated
bank account is actualized,  all arrangements have been well rehearsed and perfected on my side to guarantee the completion of this fund transfer within 14
Bank working days.
Forward your response to this email:
Best regards
Zachary Edward Noah