Mating Chlamydomonas reinhardtii

I find this paper by Jiang, X. and Stern, D (2009) published in Journal of Visualized Experiments super cool. It's about mating and separation of Chlamy's tetrad. It's laborious, obviously, but it seems to be something fun to pick up for my PhD. Let's see if it's possible... *chuckles*

Briefly, Chlamydomonas usually exist in haploid single cells, formed by the "mating" of two strains of opposite mating type (plus and minus). An explanation of the diagrammatic representation of the Chlamydomonas life cycle shown below is taken from Zhao H et al., Genes Dev. 2001;15:2767-2777 (click on the link for the full paper). Gametes are formed when vegetative mt+ and mt− cells undergo gametogenesis induced by nitrogen deprivation (middle left). When gametes of opposite mating type (or sex) are mixed together, they adhere to each other via mating type specific adhesion molecules (agglutinins) on their flagella to form large collections of agglutinating cells (upper center). Flagellar adhesion induces gamete activation that leads to release of cell walls, erection of mating structures at the apical ends of the gamete cell bodies (upper right), and several other cellular and biochemical changes that prepare the gametes for cell fusion. All of the events associated with gamete activation can be induced in gametes of a single mating type by incubating them in dibutyryl cAMP (Pan and Snell 2000b). The tips of the mating structures fuse to establish cytoplasmic continuity, and soon thereafter the two gametes merge completely to become a zygote (lower right). Zygote formation can be extremely rapid, and within 5–10 min after gametes are mixed together, 70%–90% of the cells fuse. Immediately after cell fusion, the zygote developmental pathway is initiated and at 2–4 h after fusion, the zygotes form large aggregates of tightly adherent cells (lower center) as a consequence of synthesis of zygote-specific extracellular matrix molecules and cell body adhesion molecules. At about the same time, the mt− chloroplast DNA is degraded. After an obligatory several days in the dark and upon return to nutrient-rich medium, meiosis and germination occur, and each zygote forms four progeny, two mt+ and two mt− vegetative cells (lower right). Vegetative cells undergo mitotic divisions until the nitrogen is depleted from their medium and the cycle begins again. Diagram modified and adapted from Figure 1 of Pan and Snell 2000b.

Source: http://genesdev.cshlp.org/content/15/20/2767/F1.large.jpg

Sounds fun. Enjoy watching the almost 10-minute long video. I found it rather exciting! *Thinking cap ON*

Introduction to Chlamydomonas reinhardtii

I need to write a 5-page proposal today, so I'm getting myself acclimated by doing some free writing here.

An explanation - I'm switching department and supervisor for the rest of my PhD. A difficult decision to make after spending (almost with futile effort) almost 10 months in BioAnth. It's not that I hate human evolutionary genetics, but it's not my cup of tea. So, upon discussion with various people, especially with my current supervisor and college graduate tutor, I embarked on the search for a new project, new supervisor, new department... Hard to bid goodbye, but it's better for everyone, especially for myself. I've nothing to lose in the first place, except some loss of time, but it's for the better.

If the official approval is granted, then I will be joining Professor Howard Griffiths' lab to work on Chlamydomonas reinhardtii together with an awesome team to eventually contribute to the CAPP (Combining Algal and Plant Photosynthesis) project.

An brief introduction of this species which we work on - the Chlamy:

Source: http://upload.wikimedia.org/wikipedia/commons/1/19/Chlamydomonas_TEM_04.jpg

If you could see the area which is densest in the TEM photo, that's our group's interest. The pyrenoid story. There are various aspects which we are looking into, but for now, it shall be a suspense, as it's time for me to run back to the proposal.

Yes, I'm a happier me after the 10 months of struggles, though I'd have tonnes of work to be completed in lesser time than others. Yet, I am still happy and glad. I am thankful to God for answering my prayers and to St. Jude for interceding for me. Miracles do happen, if we also work in tandem with Him.

Stupid Fish, Really??

It is hard for me to explain my current situation openly right now, but tonight I shall listen to Einstein. 

Hear ye all my fellow PhD friends out there! Dear Einstein and his wisdom!

Source: http://om.symphonyoflove.net/wp-content/uploads/2014/09/Albert-Einstein-Everybody-is-a-genius.-But-if-you-judge-a-fish-by-its-ability-to-climb-a-tree-it-will-live-its-whole-life-believing-that-it-is-stupid.jpg

Ubuntu on VirtualBox

I began to realise the need to eventually get a computer with Linux/Mac OS since many of the softwares developed for genomic analyses are Linux-based softwares. Though I might be an ardent supporter of Android phones and Windows 8 computers, for the sake of work, I probably am going to request for money to buy a computer with Linux or Mac environment.

Right now I'm in the midst of the troubling question if where I am currently is matching to my real interests. I felt ashamed, fearful and disappointed that I am where I am right now, and it didn't help when everything I proposed didn't work and I don't seem to be very enthusiastic about this. I know it is a sign I am not suitable to be in this area of research, as much as I wish to feel belonged here.

Back to what I've learned for the past nine months... More aware of computer language for sure. I might not speak any particular language yet. I am at beginner's level in Spanish and Japanese if I were to compare to "speaking" Python 3 and R.

Right now I'm installing Ubuntu on Virtual Box with the help of wikiHow's instruction. Very precise and convenient indeed. Now I can try to install some of the softwares which I desire to use. Let's see if it works.

My Windows desktop with Ubuntu running on VirtualBox

Wimpy = Small & Weak

At times, I am tempted to change my blog address to something else because the definition of "wimpy" according to Urban Dictionary is small and weak. Right now, I am feeling small and weak, with the recent wave of uncertainties. I had difficulties since the start of my PhD to form research questions and to grasp the bunch of theories formed by evolutionary biologists when it comes to whole genome studies of different populations, both the modern and archaic genomes. It was the first time I heard terms such as coalescence theory, Mal'ta Boy, Denisovan, neanderthals, plink, balancing selection, permutation, imputation, and so many other terms. It was a foreign field to me, which I honestly thought I'd be able to make it through even though I felt stupid the moment I joined the first team meeting. As what everyone in the team, including my supervisor, told me, I would eventually know while reading up. No idea which papers to start with, in fact, I abandoned reading papers for the first three months because I wanted to catch up on the definitions. I couldn't even comprehend a simple term, let alone the big theory behind it.

And I ended up feeling stupid and helpless as each day went by silently. I used to describe myself as the kindergarten kid working with a bunch of highly intelligent graduate student when I started, and some of you might know from one of my first few posts that I was ecstatic when I saw myself creating a plot using R when I did some tutorial. It didn't stay for long, because I was still so behind.

Source: http://mentalfaculties.files.wordpress.com/2013/05/student-depressed.jpg

By April, I was being asked to give a format of how I envision my PhD thesis to look like, and what research topic I want to scrutinise for the next three years and to form a set of specific research questions which I want to ask for the research topic I want to do. It didn't help to be constantly reminded I only have three years of funding but almost nobody in the department could finish their PhDs in three years, and that I couldn't expect the department is able to fund me in case I couldn't complete it within three years.

I proposed the first topic to look into the ancestry information markers using SNPs since there's still a gap to have a standard set of SNPs for world wide populations, just as how STR markers had evolved to be. It was rejected right after I said the final word of what I thought because the lack of expertise of supervising me and the group is doing EVOLUTIONARY studies, hence I should focus on something along selection, etc. Let's just say, I'm not fond nor knowledgeable of this, but if required, I can try. Provided I get enough support from the group. As if there was any to begin with.

Then the malaria topic came into discussion and I became quite fond of it, despite the fact that all I could do with it was the selection studies of the affiliated genes using population dataset without any phenotypic information, nor epidemiological information. Assumptions would have to be made. ALL THE TIME. However, when I started presenting research questions, everything I proposed was either too generic, not specific, someone had done it so it is of no interest to study it again, impossible, or insignificant. I was at loss after being in the condition for more than a month.

Source: http://drhurd.com/wp-content/uploads/2014/06/Depression.jpg

The typical question when one meets another is "How are you?" without expecting anyone to reply anything other than "I'm fine" to them. This is probably the most hypocritical question in the whole world. It sounds better to exclaim "Today's weather is ..........." to initiate conversation than to use that question. After months of telling people "I'm fine" when the truth wasn't at all fine, my barrier caved in. I sought help first from my supervisor and the college graduate tutor. To my supervisor, I was honest that I might not carry on with a 95% bioinformatics PhD for my lack of skills, and I'm uncertain if I'm suitable for this field. Same goes to my graduate tutor. Initial suggestion of the tutor at college is to talk to my supervisor. When I spoke to my supervisor about my fears, he suggested a change from the 95% bioinformatics to a lab-based project with basic bioinformatics. No more looking into malaria though. My two months worth of effort turned into ash in a single hour. I wasn't fully convinced, for there's the ethical commission approval to apply both in the university and locally, travel research grant (I don't possess wings to fly nor rich parents), and that very set "research questions". The assumption made about me was simple: "I must have had read a lot so I would possess ability to form research question by now". I could only smile feebly, because the truth is I might have been reading the wrong stuffs all together, since there's no basic guideline for PhD students on what kind of papers I should read to get an idea of what's happening. Especially someone without any basic knowledge of evolutionary biology of any kind.

After speaking to a few people, I felt more encouraged to tackle the challenge to collecting new samples, so I contacted a few people to see if they could help and some email addresses were passed to me for initial contact. Guess what? All the suggested populations were told to me as "not interesting if you still insist on doing malaria" and "it would take a long time to apply for ethical approval so in the end it would be impossible".

I am disappointed and hurt and lost. I have no project, no research ideas, no research questions... When I wrote to graduate adviser of the department informing my struggles with this PhD situation and the uncertainty if I am in the right research area, as he is dealing with family crisis at the moment, I was told that the department is shorthanded so there wouldn't be anyone who can supervise me. I am free to look outside the department for other projects or supervisors. Every time I recalled this email which I received, I cried. So this is what departmental support is like. Great.

My college graduate tutor recommended me to see the college counselor to have a chat about all these. I saw her this afternoon, and would be seeing her for a few more weeks to work out some of these things. Thank God for all the listening ears I have for the past two weeks. I am glad to have some people who still see me as someone who is capable to be here, when I no longer see myself that way. Dealing with this current issue in my PhD has caused me to lose confidence in myself. I know God is with me in this, despite the fact that some people think that religion is silly. I would have long committed suicide if not because God has been journeying with me all these whiles as I dealt with various issues in my life.

Indeed I am weak, I am a wimpy scientist, and I am stopping the pretense that I am fine, because the truth is I am not and I need help and support. Yet I know, there must be a way out. Even if it means I would have to change department, change project, spend an additional year to get things done, more extra hours and all, if this is the way out, I will walk it through... God is there. He brought me here, He will definitely see me through it.

Source: http://www.word-picture.org/wp-content/uploads/2013/07/b.2Corinthians12.10.jpg

Night Owl or Early Riser?

These days I'm finding it tough to stay awake in the day time and to fall asleep at night. A bit of a mess but I guess it's normal for any graduate student to go through such phase. For a while I identified myself as a night owl, working better after sunset. Then I found joy in rising early and sleeping early. What came next was I screwed up my own biological clock by not being disciplined. I can't be both an early riser and a night owl but the greed of wanting to buy more waking time to get something done tend to mess up the circadian time of this poor body. Outcome would always be the phase where I have to deal with my weird and unproductive sleeping pattern. Ha ha ha!

It takes a while to sync back to norm. I do recognise the importance of sleeping at night. Working from home these days doesn't help with regulating sleeping pattern or discipline on when to work and when to rest, since my life is entwined in the research which I want to do, which is a series of things done while sitting in front of this laptop. Reading papers, or working on my R skills, or figuring some stuffs out, or feeding my enthusiasm of picking up Korean language while watching yet another an episode of Korean drama, or having a meal. Leaning towards a very unhealthy lifestyle, but that's life of many graduate students. It's an amazing cycle of sleep, eat, research, eat, sleep. I sometimes wish I have lab work which would force me to walk out of this comfortable and warm nest fully equipped with the right lighting to work. Yet, I probably have my whole lifetime ahead to work in the lab in future.

Probably lots of coffee would help with staying awake in the day? Or maybe I should just quit coffee? Nah... Life without the coffee aroma... is a loss.

Source: http://my.englishclub.com/profiles/blogs/early-bird-or-a-night-owl

I guess right now it's more important to get myself on my feet with some regularity of work hours. It is getting back at me, this weird schedule and sleeping pattern.

I should blog about something technical which I sort of picked up last month. Interesting personal achievement which I forgot to pat myself and reward myself for doing it right.

Time for lunch!

Budget, Scholarship and Happy Graduate Student

Yes, I know I need to do my work, but I can't help but to write this post.

In my previous post, I mentioned I am just a poor scholar here at Cambridge. I compared my currently scholarship with the Erasmus Mundus masters scholarship which I received for the past two years, which was a very handsome amount of money. I know this can't be compared. The payment system is different. I used to receive monthly scholarship allowance, plus mobility fund every start of 6-month term. I was pretty much able to spend when I needed to.

Source: http://i.telegraph.co.uk/multimedia/archive/01811/cash_1811300c.jpg

As for now, my scholarship installment comes thrice a year. It means I get 4 months worth of scholarship allowance in one-go. It gets dangerous when the mind is switched to "I have tonnes of cash to spend" thought. It took me about 6 months to psycho myself back to the mindset that I am not as poor as I think I am. If I budget properly, I can stretch every penny I have for food, entertainment, transport, travels, and SAVINGS.

I find this article on "Student MoneySaving Checklist" highly useful for those who need some ideas on how to stretch every penny we have. What I do is within the checklist of 50+ items of how to save as a student.

Source: http://www.studentuniverse.com/student-blog/wp-content/uploads/2012/10/budgetingpiggy.jpg

Yes, I do monthly compulsory savings. And no, I don't touch the money at all. That's my emergency cash in case I need to fly back to Malaysia at any point of my graduate studies. It is still not enough to fly back, but if I start touching it habitually it, it'll never be enough. I am using Llyods Bank, and the best thing is I could have three different accounts under the same name, so I started a compulsory savings account which the money from current account is auto-debited monthly. I also have a savings account for all the accommodation money I need to pay per term. My current account is almost always out of cash, with the lowest I got to was about £10 in it (end of the month kind of situation).

It's not easy to start budgeting, but once we get the feel of it, we'll be living a happier graduate student life!

P/S: I still do get to travel a bit with the limited budget I have...

I saw Giant's Causeway in Northern Ireland end of June 2014, thanks to the budgeting I made from the start of the year.

Coffee and Graduate Students

As I venture deeper into the journey of a graduate student, I find that coffee becomes a part of my life, as much as I don't want to be "addicted" to it. I'm trying to deny the fact that I might be a coffee addict at heart, refraining myself from overdosing since the forensics background I've accumulated reminds me anything too much isn't good for me. So far, I'm fully aware that any caffeinated drinks from Nescafe would cause me drowsiness. I suspected the case when I tried staying awake to study using Nescafe Gold (yes, I only go for the best stuffs) but I ended up sleeping for hours after that cuppa. It didn't help me to study more, but my body was indeed well-rested due to the blood-pumping caffeine.

When I speak to my graduate friends, I noted that almost everybody (shy those who are allergic to caffeine, and those who drink tea like water) would have at least a cuppa a day. Some would be at the extreme of consuming more than 6 cups daily. On average, about 2 to 3 cups. As for myself, it is once a day, in the morning when I have my breakfast, usually around 9ish. Today I woke up late so I got my brunch by 11am. According to this website, the best time to drink a cuppa coffee is between 9.30 am to 11.30 am.

The initial realisation came when I stopped by Costa in Grand Arcade daily to grab a cuppa on my way to the department. I tried to be more environment-friendly, so I bought its travelling mug. Uh-huh... it stuck with me for two weeks, and I noticed how my purse bled to death. I am but a poor scholar, honestly. Money should be spent on real, filling food. So I had to think of alternative... While Costa can be my choice when I hang out with friends. Always - the hazelnut flavour!!!!

Source: http://upload.wikimedia.org/wikipedia/en/thumb/4/42/CostaLogo.svg/1024px-CostaLogo.svg.png

I was deciding between a coffee maker and a cafetiere. I chose the latter, not because I couldn't afford it but due to the fact I don't have much table top space to keep it. A stainless steel Grunwerg 3-cup cafetiere quenched my thirst of brewed coffee. Adorably shiny little thing that my heart fell in love with. Got it from Amazon using the prize money I got for being the kid with best performance of my MSc. degree. Wheeeee!!! Now I can have non-instant coffee at home. Whenever I want to.

Source: http://ecx.images-amazon.com/images/I/21ovJ5WYYcL.jpg

Initially I stick to ground coffee from Costa, as much as I like it fresh, it's not the same as what I get in the shop. Of course, no frothy milk to accompany with it does make a difference. That's when I re-discovered my love for OldTown White Coffee (hazelnut flavour) from my home country, Malaysia. Yet, a pack only consists of 15 sachets, and I died when I found I was left with one sachet the first time my ex-student brought my "supply" from home. Thank God for my kind-hearted best friend who came back for his graduation, I received two packets. And from a friend who finished her Mphil, I inherited her leftovers. Yippee!! That will keep me going for a while. But I need to look for alternatives...

Source: http://i01.i.aliimg.com/wsphoto/v0/669333435/Malaysia-import-old-town-Old-Town-White-Coffee-Hazelnut-flavor-instant-3-in-1-600g-horse.jpg

One random shopping day at Tesco Extra in Bar Hill, I saw this lovely red packet of ground coffee with the label "Hazelnut". I don't know much about this Edinburgh Tea and Coffee Co. but I supposed the price reflects on its quality. It was priced at £3.70. Not expensive, but higher priced than others. I finally made the first cup today. Completely took my heart away. I've found the non-sugary alternative to my OldTown White Coffee.

Source: http://coffee4.me/wp-content/uploads/2014/04/Edinburgh-Tea-and-Coffee-Company-Hazelnut-Ground-Coffee-227-g-Pack-of-3-0.jpg

So, I shall continue my work now. Till then... Have a cuppa!


P/S: Many would agree with me, right??

Source: http://phdcomics.com/comics/archive/phd070513s.gif

PLINK for Windows

As I'd have to pay for every Gigabyte of internet used, I was a little concerned about working in the comfort of my room. The move to a room with larger window overlooking the backyard where a couple of squirrels and a pair of pigeons reside at the pine tree really helps with a better working at home environment. I'd need to work in the department once in a while, but the alternative is as good as the office, so I feel comforted. And finally, a more sturdy desk chair is provided to me today! Yay!

This is the view from my desk: perfect, isn't it? Getting back to work :)

Back to the topic, since I'm using a laptop installed with Windows 8.1, I was thinking of running PLINK on the laptop, provided I have enough HDD space and RAM, of course. I think with 6GB of RAM, I should be able to do quite a bit before I crash it. A tiny search on PLINK website led me to the MS-DOS version of PLINK, which means I could do the genomic analysis offline without using my group's server! Another yay!

Here's the instruction as per PLINK website on how to download and install PLINK on Windows... I think the links on my page would lead you to the download site, further instructions and manuals for PLINK. Enjoy using the whole genome association analysis toolset!

This page contains some important information regarding how to set up and use PLINK. Individuals familiar with using command line programs can probably skip most of this page. Download PLINK is now available for free download. Below are links to ZIP files containing binaries compilied on various platforms as well as the C/C++ source code. Linux/Unix users should download the source code and compile (see notes below). These downloads also contain a version of gPLINK, an (optional) GUI for PLINK. Please see these pages for instructions on use of gPLINK. Remember This release is considered a stable release, although please remember that we cannot guarantee that it, just like most computer programs, does not contain bugs... Platform File Version Linux (x86_64) plink-1.07-x86_64.zip v1.07 Linux (i686) plink-1.07-i686.zip v1.07 MS-DOS plink-1.07-dos.zip v1.07 (to be posted later today, 30-Oct) Apple Mac (PPC) plink-1.07-mac.zip v1.07 (to be posted next week) Apple Mac (Intel) plink-1.07-mac-intel.zip v1.07 C/C++ source (.zip) plink-1.07-src.zip v1.07 One more thing... If you download PLINK please either join the very low-volume e-mail list (link from Introduction page) or drop an e-mail to plink AT chgr dot mgh dot harvard dot edu letting me know you've downloaded a copy. For old versions of PLINK please visit the archive. Debian users PLINK is available as a Debian package, see these notes. Note, the executable is named snplink in the Debian plink package. Development version source code You can download the very latest development source code in this ZIP file. This is really, strongly not recommended for most users. The code posted here could change on a daily basis and is not versioned. Development source code versions have a p suffix, meaning pre-release. For example, if the current release is 1.04, the next stable release will be 1.05 and the development code will be 1.05p. Note that 1.05 may differ from 1.05p and as noted before, from day-to-day the 1.05 development code may change in any case. The principle reason for including the source code here is to allow access for specific users to specific, new features. These features are described here. General installation notes The PLINK executable file should be placed in either the current working directory or somewhere in the command path. This means that typing plink or ./plink at the command line prompt will run PLINK, no matter which current directory you happen to be in. PLINK is a command line program -- clicking on an icon with the mouse will get you nowhere. Below, on this page, is a general overview of how to use the command line to run PLINK. The next sections give details about how to install PLINK on different platforms. Windows/MS-DOS notes Unzipping the downloaded ZIP file should reveal a single executable program plink.exe. The Windows/MS-DOS version of PLINK is also a command line program, and is run by typing plink {options...} not by clicking on the icon with the mouse. Open a DOS windows by selecting "Command Prompt" from the start menu, or entering "command" or "cmd" in the "Run..." option of the start menu. The folders c:\windows\ or c:\winnt\ are typically in the path, so these are good places to copy the file plink.exe to. You can copy the plink.exe file using Windows, as you would copy-and-paste any file (e.g. using the right-button menu or the keyboard shortcuts control-C (paste) and control-V (paste). Alternatively, if you know that you will only ever run PLINK on files in a single folder, then you can paste plink.exe into that folder, e.g. C:\work\genetics\. The disadvantage of this approach is that PLINK will not be available from the command line if you are in a folder other than this one. Once you have copied plink.exe to the correct location, you can test whether or not PLINK is available (i.e. in your command path) by simply typing plink at the command line. You should see something like the following message: Microsoft Windows XP [Version 5.1.2600] (C) Copyright 1985-2001 Microsoft Corp. C:\>plink @----------------------------------------------------------@ | PLINK! | v0.99l | 27/Jul/2006 | |----------------------------------------------------------| | (C) 2006 Shaun Purcell, GNU General Public License, v2 | |----------------------------------------------------------| | http://pngu.mgh.harvard.edu/purcell/plink/ | @----------------------------------------------------------@ Web-based version check ( --noweb to skip ) Connecting to web... OK, v0.99l is current *** Pre-Release Testing Version *** Writing this text to log file [ plink.log ] Analysis started: Fri Jul 28 10:07:57 2006 Options in effect: ERROR: No file [ plink.ped ] exists. Do not worry about this error message -- normally you would specify your own PED/MAP file names to analyse (i.e. the default input filename is plink.ped). Please ask your system administrator for help if you do not understand this. HINT In MS-DOS, you can to increase the width of the window to avoid output lines wrapping around and being hard to read. To do this under Windows XP DOS: right click on the top title/menu bar of the window and select Properties / Layout / Window Size / Width -- increse the width value to a larger value (e.g. 120, or as large as possible without the window getting too big to fit on your screen!).

Anxiously Taking Off...

Source: http://upload.wikimedia.org/wikipedia/commons/6/64/Malaysia_Airlines_Boeing_777-200ER_9M-MRO_IST_2012-1-23.png

Finally, after 6.5 months, the first phase of my PhD is sort of taking off. I hope that this first phase will reach its final destination of a first year report which enables me to officially become a Cambridge PhD student, rather than the current probationary status. This post also serves as a tribute to all the passengers of MH370, the aircraft which also the last location where my cousin worked as the cabin crew. Despite not knowing him well when he was around because of our large age gap, I know David, my cousin, worked hard his whole life, and went through various struggles. He never gave up on life, on love. I wish I can learn this attribute of his.

I am nervous, and anxious too, especially after such a long hiatus on research due to my health, the travels, and the graduate conference (as much as I tried to deny the fact that I did put in much time and enjoyed doing it). Sometimes I dislike the fact that I could catch a cold too easily, and with the new addition to my medical history of acute sinusitis, my sinuses become infected twice this year alone. All these took time away from me trying to work hard because I sleep for days. Right now, I am worried I can't meet the par of passing my first year though I have another 3 months before the reality sets in. What if I have to go home because I can't complete year 1 and pass this probation? Everyone knows he/she has worked hard for a year, so it is natural passing first year isn't difficult. For me who spent most of my time sleeping and idling, it is as natural as them, only I'm at the other side of the fence. Working hard is not my forte. Yet, I know it takes hard work whether or not I'm good at it.

I saw this online when I was searching for the quote... "Don't be upset with the results you didn't get from the work you didn't do".

Source: http://www.savingadvice.com/articles/wp-content/uploads/2013/08/insecurity.jpg

I guess me browsing through the Wellcome Trust Sanger Institute is a cause of my anxiety. There is a group who is doing an awesome job with malaria. I saw their papers and found those interesting. Who am I to compare to them? All highly-skilled bioinformaticians and biologists; big brains gathering big data as a team of researchers. I need to overcome this insecurity I feel from within, really.

This is my behind-the-scene, nothing too bright or shiny, as how anyone would see a Cambridge graduate student should be. We all are still graduate students, just like anyone else in the world. We struggle too, and maybe, more than the rest of the world.

Graduate Studies at Cambridge

I wrote an article to be included in the graduate section of Outreach 2014 booklet of Cambridge University Malaysian Society as the committee prepare themselves to reach out to the students who might want to apply to Cambridge for the next academic year.

For the academic year of 2013/2014, 37 Malaysians out of the 158 who applied to Cambridge received confirmed admission to graduate courses ranking 11th among the other countries with success rate of 23%. There are two categories of qualifications for graduate studies: courses with taught elements, and research programmes. Either category, the best way to research on the available programmes and the criteria of admission is via the Graduate Admissions website of the University of Cambridge.

A little about applying to graduate studies at Cambridge:

It is crucial if you are planning to apply for research programmes to communicate with your potential supervisor to find out more about the research group and the interests of the group. It doesn't bring any harm to have a clearer idea of what the expectations of your supervisor are before you apply. Also, it also helps you in your decision-making process. Apply for admission only when you are certain that your potential supervisor is keen to having you. Online application makes it so convenient! As my basic degree was awarded by Malaysian university, which was not conducted fully in English, I was required to submit proof of English competency. The accepted English Language Tests include IELTS (International English Language Testing System) Academic, CAE (Certificate of Advanced English) with grade A (with other conditions to fulfill) or CPE (Certificate of Proficiency in English) with grade A or B. TOEFL is NO LONGER accepted according to the Home Office requirement. Minimum required score is according to the course applied. In the application for research programme, a research proposal would be required, and this can be discussed between you and your potential supervisor.

Other than that, it is important to take notes of the deadline of applications to funding and scholarship. If your potential supervisor has a research grant to sponsor you, then it is wonderful. If not, you might want to research on other available scholarships, as well as to apply to the Cambridge Trust fund and Gates Cambridge scholarship when you apply for admission. Usually the deadline for the latter two is around December.

In my opinion, the important elements to successful application include: 1) Excellent English competency, 2) acceptance of your research proposal by the department which you are applying to, 3) acceptance by one of the colleges, 4) financial conditions. Be meticulous and prompt with the list of conditions to fulfil the admission process!

Once all the conditions are fulfilled, the Graduate Board of Studies will award you with the offer letter and CAS for you to apply for Tier 4 student visa. The CUMaS community will be at Cambridge waiting for your arrival.

A little on the life of a Cambridge graduate student:

During the High Table in the college...

I completed my BSc. (Biotechnology) in University Malaysia Sabah and hold the Erasmus Mundus Masters in Forensic Science awarded by the consortium of host universities (University of Cordoba, Spain, Egas Moniz University, Portugal, University of Lincoln, UK). The university systems which I had experienced previously were different from my current experience here, as University of Cambridge is a collegiate university, and all students are members of a college. I am a member of Fitzwilliam College. Usually graduate students would be offered a room in the college, either in the main college site or the college houses. From what I know, all colleges provide housekeeping services to college accommodations. Each college has its own traditions and system, which you could read more on its website. At term time, Fitz organises formals twice a week and members of the college who wish to attend the formal could make reservation via our college account. Once a year, the graduate students are invited to dine with the Master and fellows at the high table. I am assigned a graduate tutor in the college whom I try to meet at least once a term for a chat. Also, graduate students belong to the Middle Combination Room (MCR) community of the college, where the MCR committee would organise events for the graduates in the college. The MCR room of Fitz is housed in the Grove, which used to be the abode of Emma Darwin, the wife of Charles Darwin. I find my college a very friendly yet conducive environment for my stay as a graduate student.

Besides my supervisor, I have been asked to nominate a secondary adviser according to the statute of the university. All research work is being supervised by the department. Being in my first year, I am still a PhD (probationary) student. Only upon submitting a first year report and passing it would I be a proper PhD student. I look forward for the day to come end of this year! Though it takes a lot of hard work to be a graduate student of Cambridge, it will be worthwhile to work in an environment so conducive and supportive of on-going research.

For more information about graduate admissions, please visit this website:

http://www.admin.cam.ac.uk/students/gradadmissions/prospec/

The Big Q

Finally, I've arrived to the stage of forming the Big Q for my PhD research! *tears of joy*

MALARIA shall be my journey for the next three years (and whatever that might pop up as this continues).

I have a report deadline in 1.5 hours with the MA to earn the upgrade from "cause for concern" to "fair" on his supervisor report. Scary!!!!

Source: http://www.euvaccine.eu/sites/default/files/uploads/images/diseases/EVI_Pf_cycle_logo_110225.png

Big Brains or Big Data??

My team and I have worked for the past few months to gather the best speakers and promote this upcoming conference (Friday, 27 June 2014). We'll have two speakers speaking to audience in Cambridge from the U.S., one of them being the Research Director of Google Inc. To find out more about our conference, visit our website "Evolution of Innovation: Big Brains or Big Data?"

Literature Review

In the midst of searching for the light at the end of a dark tunnel, I begin to wonder how to do I wade out of the marshland of "Hows?". I know more reading, and more questioning, might help the process. And I wish for more shortcuts to understand the papers I'm reading as I form that big Q. It seems to me that everybody seems to have a relatively easy time to form the big research Q, minus me. When will I be able to form a proper big Q which is good enough to impress the MA?

Source: http://static2.quoteswave.com/wp-content/uploads/2012/01/The-big-question-is-whether-you.jpg

Everyone has his own method of literature review. Mine may not be the latest method. This is just what I know and most comfortable with. Let's return to MY way of systematic literature search:

1. I start with the journal which is directly related to my topic of interest.
2. Chronologically, I chose to start from the latest discoveries - some research paper with direct interests which seems pretty similar to my research group's methods of interest.
3. For more comprehensive understanding of the topic, I choose the latest review paper.
4. It is important to take note of the list of references of those papers I am reading.
5. More reading, and note taking.

This is a method I found published on the student support website of UCLan..

Source: https://www.uclan.ac.uk/students/study/library/literature_search_tips.php

I'd recommend the use of Mendeley desktop to aid the walk in the forest of references. So far I find using a reference manager very helpful and systematic. Others might have different recommendations.

One's Beauty Might be Another's Thrash

Source: http://files2.coloribus.com/files/adsarchive/part_1095/10957605/file/solitaire-anti-reflective-coating-rubbish-dump-large-86735.jpg

My recent input of research questions is officially thrash which is deemed unfit to be done at this point. Too backwards, pointless and over-simplified for this group I'm in. I wouldn't say what I want to do is something stupid, it is just more industrious rather than academic, more focused on forensics than evolutionary. So it's unsuitable, and uninteresting from another point of view. So, bye-bye full-on forensics genetics for now. I guess this can't be help, when I'd rather try to find what would cost less for a third world, developing country to apply, where I am placed right now has excellent methods, human resources, and hardware to execute sophisticated analyses. I guess I need to discard the third-world mentality and embrace sophistication for now.

A negative progress is still a progress. Indeed. It is.

Positive Workplace Attitudes

I'm under a lot of stress trying to come out from the state of stupidity and uncertainties (with not much progress these days). I'm trying to grab as many hours of solo working as I can in the office with perfect lighting for work. It means asking an owl to wake up and hunt in the morning. Not much of choice, since morning is the best time to work as there is practically nobody in the office before noon!

Source: http://images.fineartamerica.com/images-medium-large/sleepy-owl-mandy-wiltse.jpg

I've recently saw an infographic which I found rather useful as some form of self-motivation. I don't have anyone who would "be there and support" me no matter what happens. Nope, nobody could truly understand the estrange condition and dysfunctions of that institution/structure of which I am a permanent member (not by choice). So, I only have God as my only source of strength, and yes, friends who have been my friends long enough that they are my family, my spiritual home. When I go through difficult times, the thought of God is with me (c.f. Psalm 46:10) helps me go through those periods.

Here's something everyone could do with, rather than complaining all the time of that workplace situation, make a difference by making a change in our own life!

Source: http://designtaxi.com/news/366397/Infographic-18-Ways-To-Be-More-Positive-At-Work/

I'm not perfect, and never will be. All I hope is I could complete this PhD and go on doing something which makes a difference in my battered life and in the lives of others.

The Fifth Month of PhD

In another seven months, I will either be deported back to Malaysia without completing a PhD, or successfully passed the benchmark of first year. I have three days before hitting the end of my fifth month here at Cambridge, and entering the sixth month of this caffeine-pumped, worries-filled life of mine.

Developing a proper research area and questions is something which has been bugging me since day one of my PhD. I know everyone is worried, especially the Man Above (MA). I do have some ideas forming at the back of my mind right now, but I'd have to test them out before talking to him. MA is a kind supervisor, but it is due to my own guilt of not doing enough that I find him fearsome. I guess I'd have to slowly work out that fear and guilt I feel within me when it comes to speaking to MA.

I'm still keen on doing forensics-related research which has connection with my team's main work on Molecular Evolutionary Genomic Analysis. It all has to do with my previous Masters research on DNA profiling. It is all possible, but I'd need to read more before presenting the baby to him. Let's just say I'm interested in the works on Kenneth K. Kidd for now...

Source: http://blog.illumina.com/img/dna_mag_300.jpg

Toolkit Story

Everyone needs a personalised toolkit in order to achieve their goals.

A surgeon needs his tools and team to ensure his patient can undergo a safe and successful operation under him.

Source: http://upload.wikimedia.org/wikipedia/commons/0/08/Surgeons_at_Work.jpg

An artist needs his brushes and paints and canvases to produce beautiful paintings.

Source: http://columbiametro.com/images/cache/cache_3/cache_d/cache_c/3dc8a408a597b5d093d73c57cc67ea3a.jpeg?ver=1400749198&aspectratio=1.5

A mountaineer needs reliable mountain gears to ensure he arrives at the top of a snowy mountain safely.

Source: http://www.mountainguides.com/photos/gear/backpack-tahoma.jpg

As for me, a PhD probationary kid, I need to achieve part of this network of computational biology.

Source: http://compbio.mit.edu/teaching.jpg

So, the first step is to understand what it is all about, and to find the right tools to start working on it. It seems to me that I am looking more into the area of computational genomics in the sense of biological anthropology these days, so there are a set of tools (packages or whatever one would call that) which I can pack in my imaginary backpack to get me going.

Source: http://www.compbio.cmu.edu/images/background.gif

Will I be able to form a proper research question by the end of my 6 months here? I have another month to ponder about this. While pondering, more packing to be done for the next chapter of my journey...

Source: https://cord-global.terradotta.com/_customtags/ct_Image.cfm?Image_ID=57

PH525x Data Analysis for Genomics

Source: http://media-cache-ec0.pinimg.com/736x/ac/5d/b1/ac5db17580e6bd3ad70f2584b0cb3cc8.jpg

I need a change of learning pace. I've realised it for a while now, but yes, I procrastinated like crazy and persisted in stubbornness. Ahh... well, yeah. I've heard about edX a while ago, but thanks to the procrastinator who lives in me, I've delayed utilising this very good website properly. It is high time to enter into a learning frenzy before I fly off to Krakow next Thursday.

I've signed up for two courses, one is "Data Analysis for Genomics". This program is conducted by Professor Rafael A Irizarry and Dr. Michael Love from Harvard University, which is the founder of edX. Actually the course started on 7th April but I signed up to audit for this course a few minutes ago. Fingers crossed it will help me in my PhD. I'm a bit desperate, but I guess being desperate right now can be a good thing rather than being desperate at the end of my first year not knowing if I'll successfully proceed to my 2nd year or not.

You could find out more about this leader of an online learning movement, MOOCs (Massive Open Online Courses), on their website (click on the edX image below). As mentioned, the founders of edX are Harvard University and the MIT (Massachusetts Institute of Technology). edX offers online college courses to everyone and anyone in the world. I guess the only reason one will not learn is when one decides not to learn.

So wish me luck and pray for me!

Cheers!

Writing Your First Year Report

I attended the course conducted by Dr. Geraint Wyn Story for GSLS (Graduate School of Life Sciences) PhD students to learn how to write my first year report. I know it is still a few months away before I start freaking out totally about it, but I guess it is better that I prepare myself right from the start rather than stressing myself out not knowing what I need to do when it is time to submit that very report which will determine if I stay or leave Cambridge. To be honest, I am freaking out already despite the fact that the first year report seems to be a very informal event in the division which I am in. Furthermore, the man above has been pushing me to produce results. I feel like a child who is asked to run when I am still learning how to crawl. Yes, the sense that I am stupid exists, and I feel very real about it, though I am more assured after attending the session that it is alright to feel how I feel.

One thing which is encouraged in developing our writing skills is to write regularly as a on-going process. A new concept (maybe not-so-new) was introduced -- "Writing to Prompts". This concept uses question or fragment of a sentence to stimulate the writing process. I do find it beneficial as it helps to focus our mind into writing something. Personally, I tend to break down the things I want to write into subtopics, and then explore the literature and read them accordingly, sometimes making notes based on sections of the same paper.

Another interesting idea is to do "Free Writing" of about 5-10 minutes with a suggested ideal frequency of 3 times a week. Writing without stopping for a duration of time on a certain topic indeed will help to free-up the writer who is bogged by the research and improve self-confidence. When we practised this concept, I came up with a short entry on "First Year Report Training".

One more concept before I end this post is the introduction of "Writing Groups" to act as a social activity plus an encouragement to help us write, and to make writing fun. Anyone would like to be my partner in crime for this?!

The usual culprits of a good report would the standard format, and everything else is rather dependent on the department. First year report should focus on introduction and future works with some prelim results and methods if there is any. A little about referencing was covered, and the importance of knowing who will be reading the first year report, and who are the examiners, plus the importance of appointing a secondary adviser. Gantt's chart is suggested to be a part of the first year report to give an idea of the audience what I plan to do.

This takes a bit of my time to digest it.

I'm ending this with something from PhD Comics. Cheers!

Source: http://www.phdcomics.com/comics/archive/phd030712s.gif

First Year Report Training

The day was gloomy when I woke up after the multiple alarms went off. It was a dread to try to wake up these days but I knew how important it is for me to connect with people studying Life Sciences and to know about first year report. The people in........***censored***........... It has been a lonely journey.

After a series of missing bus, getting lost and finally getting there to listen to Dr. Geraint talking and the PhD probationary students speaking of first years' worries, though more questions popped up but I'm assured that I'm not alone in my struggle to bear future responsibility as a Cambridge grad. Perhaps it doesn't take a super genius to get a PhD done here.

There's still some time left. Let's see how it goes.

PLINK: Association Analysis / Accounting for Clusters

It wasn't one of the best days. Had a word with the man above when I bumped into him in the pantry and he didn't seem pleased that it took me two weeks to look at the paper on placing individuals in their geographical location. I'm taking very long because the methods are fundamental, but it wasn't a knowledge that I am born with, unfortunately. I've long suspected that everyone is assumed to be a genius of some sort where I am based and I did feel stupid as I am taking longer time than "most people" to pick up the basics. I know he thinks I'm too slow to learn the skills needed. It's ok, it is not the first time I felt like a complete idiot in this group of geniuses. I have been feeling stupid for a while now. This stupidity is suffocating me from within. I guess this is a price to pay to eventually able to carry the responsibility of having the Cantab post-nominal and the permanent effect of a head damage for ramming into the world of graduate life. Why in the world did I decide to do this? I no longer am in the mood of discern it right now.

Source: http://thegradstudentway.com/blog/wp-content/uploads/2012/07/PhdComics2.jpg

Anyway, back to my learning progress. Any form of progress is better than nothing at all. After the long break from learning, finally I'm back at PLINK tutorial. Today I plotted a multi dimensional scaling (MDS) plot using the HapMap example of two population.

Population stratification is the presence of systematic difference in allele frequencies between subpopulations in a population due to different ancestries, also known as population structure. Stratification analysis use whole genome SNP data to cluster individuals into homogeneous groups. In the tutorial, simple stratification was performed, but the details of it could be found in another chapter in the PLINK website. I think it is worth me spending the whole afternoon going through the main documentation on population stratification as I probably would need to perform this as a routine data treatment procedure and if I don't get it now, I won't get it later. I don't want to form bad habits in programming and jeopardize the quality of my research in future.

If two or more individuals have identical nucleotide sequences in a DNA segment, it is known as identical by state (IBS). If this segment is inherited without recombination by a common ancestor, and is found in two or more individuals, then it is identical by descent (IBD). I find that both IBS and IBD are of the few jargons often mentioned during lab meeting, so it is important that I have these two definition registered in the brain and here. The clustering which I did today was based on pairwise identity-by-state (IBS) distance clustering. No constraint was applied to the process. Usually phenotype criterion and cluster size restriction, plus external matching criteria are specified.

In order to create the MDS plot for the HapMap example of two populations, I first created matrix pairwise IBS distances using this command line:

plink --bfile mydata --cluster --matrix --out myplot

A few files were generated: myplot.mibs, myplot.cluster0, myplot.cluster1, myplot.cluster2, myplot.cluster3, myplot.log. Information are stored in different formation within the four output files resulted from performing the --cluster option.

Using RStudio (it means I used R statistical tool), I created the MDS plot with the code given:

m <- as.matrix (read.table ("myplot.mibs"))
mds <- cmdscale (as.dist (1-m))
k <- c( rep ("purple", 45), rep ("orange", 44) )
plot (mds, pch=20, col=k)

# RStudio was used on Win8 laptop while PLINK was used on UNIX server.

Here's how my plot looked like:

Very interesting combo to use both PLINK and R to generate the plot. According to the tutorial, I could also generate the MDS plot using the --mds-plot option. I have not tried it, so I'm unsure how does it work. I guess it is best that I keep to one which I will be good at, rather than to learn 101 alternatives. I am certain I can beautify my MDS plot. That I can wait.

I better sign off now. I am attending training on "How to Write First Year Report" in the Clinical School later.