CG vs. Illumina (Sensitivity)

Came across MJ's post in response to CG's post about our sequencing platform paper on Nature Biotechnology:

http://mendeliandisorder.blogspot.com/2012/03/cliff-reid-on-cg-vs-illumina.html

MJ pointed out a good point that our small set of Sanger sequencing data was only suggestive. Here is my thought.

A confidence level of 95% and a confidence interval of 5% for each of the platform specific call set requires a minimum sample size of ~380. Any further estimation based on a statistically insignificant set is inconclusive. That's why we went on to SureSelect at a larger scale, which gives us a statistically significant result.

As mentioned on the paper, the SureSelect may have potential bias since it was followed by Illumina sequencing. But if there is a strong bias towards Illumina due to systematic errors, probably the invalidation rate for Illumina itself wouldn't be as much as that for Complete.

Let's take the existing Sanger numbers and calculate it once again with its possible errors. With the same confidence level of 95% aforementioned, the possibly best validation rate for Illumina is 30% and the worst for Complete is 83%, which convert into 104K and 83K true positives in their specific call sets, respectively. That said, Illumina is still having a higher sensitivity, whereas Complete is more accurate (less FDR).

If it looks unfair, that's the problem of extrapolating on a set with big error bars. One thing that is true is that we can do a larger scale of Sanger sequencing on the specific calls, then we can have a better sense of the potential ground truth which will be less controversial.

Until then, we gotta believe that they both have their goods and bads, and performed very well overall.

Detecting and annotating genetic variations using the HugeSeq pipeline

Deciphering genome sequences is important for the mapping of genetic diseases and prediction of their risks. Advances in high-throughput DNA sequencing technologies using short read lengths have enabled rapid sequencing of entire human genomes and unlocked the potential for comprehensive identification of their underlying genetic variations. Various computational algorithms for identifying and characterizing

variants have been developed; however, most of these computational methods are neither integrated nor interoperable, making it difficult for biologists to extract all the genetic information from billions of sequences generated by these sequencing technologies. We developed HugeSeq, an integrated computational pipeline to fully automate the process of variant detection from alignment of these genomic sequences to detection and annotation of all types of genetic variations (single nucleotide polymorphisms (SNPs), short insertions or deletions (indels) and larger structural variations (SVs)).

Reference: Nature Biotechnology. 2012 Mar 7;30(3):226-9.

Performance comparison of whole-genome sequencing platforms

Whole-genome sequencing is becoming commonplace, but the accuracy and completeness of variant calling by the most widely used platforms from Illumina and Complete Genomics have not been reported. We sequenced the genome of an individual with both technologies to a high average coverage of ~76X, and compared their performance with respect to sequence coverage and calling of single-nucleotide variants (SNVs), insertions and deletions (indels). Although 88.1% of the ∼3.7 million unique SNVs were concordant between platforms, there were tens of thousands of platform-specific calls located in genes and other genomic regions...

Reference: Nature Biotechnology. 2011 Dec 18;30(1):78-82.

卡通王國

很高興阿Don同Kennis已經買了期待已久嘅卡通王國。真想不到，這個經典系列竟然沒有六神合體，相聚一刻，小雙俠。。。仲漏咗咩歌？



CD 1
01. 足球小將(足球小將片尾曲) - 張衛健
02. 美少女戰士 - 王馨平 湯寶如 周慧敏
03. IQ博士 - 梅艷芳
04. 現代足球小將(現代足球小將) - 李克勤
05. 伙頭仔昆布 - 草蜢
06. 藍精靈 - 小太陽兒童合唱團
07. 數數小精靈 (寵物小精靈) - 陳浩民
08. 龍珠 (龍珠Z) - 張崇基+張崇德
09. 黃金戰士 - 胡渭康
10. 你讓我找到未來(高智能方程式) - 草蜢
11. 新世紀福音戰士(新世紀福音戰士) -楊千嬅
12. 跅跅步哈姆太郎 (哈姆太郎) - 2R
13. 寶貝甜心 (媽媽是小學四年生) - 湯寶如
14. 忍者 (忍者小靈精) - 小太陽兒童合唱團
15. 時代節奏 (童夢) - 劉錫明

CD 2
01. 夢中天使 (長腿叔叔) - 唐韋琪
02. 我係小忌廉 - 戴蘊慧
03. 多拉A夢 - 陳慧琳
04. 問題天天都多(櫻桃小丸子) - 歐倩怡
05. 小甜甜 - 路家敏
06. 人人愛愉快 (得意快獸仔) - 楊千嬅
07. 皇家雙妹嘜 - 歐倩怡
08. 美少女變身(美少女戰士R) - 陳琪
09. 愛心一百次(飛天小女豬事丁) - 戴恩玲
10. 命運鬥士(鎧甲聖鬥士) - 張衛健
11. 神秘的花園 - 何詠琳
12. 情誼心中印 (龍貓) - 江欣燕
13. 超人小子 (超人小子) - 黎瑞恩
14. 每點愛都記住 (娛樂金魚眼) - 車沅沅
15. 降魔者 (仙魔大戰) - 劉彩玉

CD 3
01. 超人的主題曲 (超人迪加)- 陳奕迅
02. 城市獵人 - 劉德華
03. 宇宙大帝 - 張國榮
04. 千年女王 - 露雲娜
05. 魔法咕嚕咕嚕 (咕嚕咕嚕魔法陣) - 滕麗名
06. 聖鬥士星矢 - 譚耀文
07. 達爾大冒險 - 蘇永康
08. 戰士高狄安 - 蔣慶龍
09. 忍者亂太郎 - 鄭嘉穎
10. 魔法時代 (魔動王) - 曾航生
11. 跟你啄一啄 (福星大咀鳥) - 李彩樺
12. 伏魔小皇子 - 梁漢文
13. 無名小子(伙頭智多星) - 黃凱芹
14. 冰河戰士 - 黃思雯
15. 劍神傳說 (反斗劍神) - 許志安

CD 4
01. 傳說 (千年女王) - 露雲娜
02. 百變小櫻 (百變小櫻MAGIC咭) - 曾嘉莉
03. 足球小旋風 - 李克勤
04. 爆裂旋風 (爆旋陀螺) - 郭富城
05. 超速龍球 (超速搖搖) - 方力申
06. 超級小黑咪 - 陳慧琳
07. 小丸子的心事(櫻桃小丸子) - 何韻詩
08. 變出我精彩(七小花) - 2R
09. 彈珠人的愛心炸彈 (BOMBOM彈珠人) - 楊千嬅
10. 正義 (無敵3x1) - 黎瑞恩
11. 虎威戰士 - 林子祥
12. 腦波子 - 陳美齡
13. 四驅小子 - 吳婉芳
14. 一股歪風 (電子神童) - 梅艷芳
15. 海 (冒險少女娜丁亞) - 吳國敬

Birth Annoucement - Atticus

Libretto Script Blue Birth Announcement

Find hundreds of cute baby birth announcements at Shutterfly.com.

View the entire collection of cards.

Graduation and Beyond

Five years ago, I started a journey that was more challenging than I had ever expected -- gave up my work in IT and began a study in a subject that was totally new to me. I guess the most difficult thing is that, as a PhD student in the States, you will never know when exactly you can graduate until the very last minute. Knowing the nature of research, it should not be anything surprising; however, getting through it is really another matter. Like what in the PhD comics, it is absolutely not easy to see all the achievements (buying houses, getting promotions, having children, etc) of your friends in the same year while you are still a student at the ground level :-P

I wasn't sure I had made a right decision, and I am still not sure yet. Nevertheless, I have certainly learnt a lot in many aspects throughout the years, which I am sure I would not have time to learn or even think about it if I were still working in Hong Kong. With no doubt, doing a PhD is definitely a tough process. But in retrospect, its certainly an unforgettable and fruitful experience for life. So yes, by the time of this writing, I have basically graduated or otherwise I would be still complaining this and that :-) I am delighted to annouce that I successfully defended my thesis on May 20 followed by the submission of it on May 25.

So what's next? there must be a reason for taking one and a half months to update this blog :-P In the past two months, I was super duper busy not only with preparing for my graduation, but also with packing things for relocation -- because I got a Postdoc offer at Stanford starting from June. (Postdoc is actually a postdoctoral training for one to three years after a PhD degree.) So yes, I am still sort of a student, and looking forward to get a permanent job some day :-)

Last but not least, my graduation would not be possible without the support from all my friends, families and especially my dearest wife. Thank you!

My Graduation Progress

Just submitted the first draft of my thesis and the presentation for the defense to my advisor. Now waiting for confirming the date of defense and I will be all set for my PhD! Can't wait to move on and start something new in somewhere new :-)

New Way To Locate Big Genetic Variants

Finally published my paper. And its on Yale News too!

New Haven, Conn. — Yale University researchers, analyzing hundreds of billions of bits of genetic information, have collated and standardized 2,000 signposts that mark the boundaries of large blocks of human genomic variants.


See more...

Citation: Lam et al. Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library. Nature Biotechnology. 2010 Jan;28(1):47-55. Epub 2009 Dec 27.

PubMed ID: 20037582

The Dolphin has arrived

My wife has finally come to the States. After separating for almost two years since our marriage, we are now experiencing the same 'honeymoon' period like the couple months after we just got married. It's sweet, it's life. Of course, I started to have a pretty 'up-scale' catering provided, as you can see from her new blog, Dolphin-icious:

http://dolphinicious.blogspot.com/

Good Science vs. Bad Science

I find the following article quite interesting, but it is quite true. So good or bad, its up to your choice.

http://www.aps.org/publications/apsnews/200908/zerogravity.cfm

The most high-tech flight

Yes, the most high-tech flight I have ever taken - Virgin America. Not to mention the romantic blue light of the cabin, just the touch screen of the LCD display is what I have been longing. But more surprising is the Internet service on the flight! Yes, its Internet, the one that now you are using to read this blog. Can't believe? me too. I can't even believe in the quality and the pricing. How much? its 5.95 (promotion, originally 12.95) for the long haul. Just can't beat. With such a service and convenience, it's worth every penny. What more is that the whole entertainment system is so nice. Not only you can watch movie and some TVs, but also order food and drinks electronically. And for Google fans, you definitely can't miss it because it uses Google Map for GPS, fancy enough? Richard Branson, you are really changing the world! At least the way people do business.

Written on the plane from San Francisco towards New York, while flying over Iowa.

再度蜜月

兩個月的假期很快便過去了,一轉眼就離開了香港四年多的時間,實是一段很不容易的日子.這幾年間發生了很多大大小小的事情,亦有一些很大的人生轉變,包括暫停了五年多的IT工作,攻讀博士學位,結婚,等等等等.回想起結婚的種種,就好像是昨天的事一樣.今次的旅程又把我帶回了三藩市,令我不禁又想起跟太太的夢幻蜜月之旅,起點就正是三藩市.已經是兩年了,但感覺仍像昨日.雖然今次暫不能跟太太一起回美國,但相信好快就可以團聚.今次回港,不同的是幾乎沒有跟朋友會面.原因有二,一是真的希望再聚的時候可以知道自己何時畢業和未來去向,二是希望可以多一點時間跟太太相處.很開心的是令次可以跟太太慶祝生日和兩週年紀念,而且我們的週年慶祝是到廸士尼,就好像再度蜜月,浪漫非常.事在變,人也在變.一樣的三藩市,不一樣的人...這更教人要珍借所擁有的,為擁有而開心,為相聚而感恩.

Life. Lessons. Legacy.

Experience is what you get, when you don't get what you wanted... The brick walls are there for a reason. (Dr. Randy Pausch)

The best lecture which summarized the whole philosophy of life:



by Prof. Randy Pausch at Carnegie Mellon University specialized in Virtual Reality, the greatest man forever.

• The reprised: http://www.youtube.com/watch?v=R9ya9BXClRw
• The interview: http://www.youtube.com/watch?v=BZbOQqtDAW0
• Good morning America: http://www.youtube.com/watch?v=wVFmFof6aXg

Another inspiring talk, one of the best lectures I have ever seen, by Steve Jobs:

http://www.youtube.com/watch?v=UF8uR6Z6KLc

Stay Hungry. Stay Foolish.

Re: Fantastic March (夢幻三月)

The easy-come-easy-go Spring Break vacation is finally over this year. March would not be as fantastic without Spring Break, and Spring Break would not be as nice without a reunion. Though the 3-week vacation had a tight schedule (originally two-week), it was indeed quite substantial. Thanks to 'Dolphin Travel'!

So where did I go this time? Visiting friends (including bumping into couple friends) and relatives, and of course, Macau again! I go to Macau like everytime I come back to Hong Kong. No wonder Don suggested that maybe next time I should just directly land at Macau instead :-) But why I like going there so much? Well, it's the food and the relaxing atmosphere. And of course it also depends on who you are going with. Though we don't really gamble, but we do like playing the 10 cents slot machines, which is actually cheaper than playing arcade games :-P This time, we also went to a concert called gold-typhoon concert, which was a very special concert with more than 12 artists performed.




Time flies, especially happy time. Now I am back to the ordinary same old days. Work again. Not April Fools though :-( Howsoever, it shall be the harvest year finally. Good luck, good health, and best wishes for everything to you and me!


In response to post: http://mypaper.pchome.com.tw/news/carinna/3/1312472169/20090331173935/

09 Spring Break - 牛年春假

真係一年容易又Spring Break。不知為何讀書比做工來得更要忙碌，更大壓力。可能因為讀PhD根本就是沒有真正的休息和假期(尤其是思想上)，如果不是“神童”或Ivan或equivalent，也很難會有真正的假期. 無論如何，假總是要放，縱使是帶著千斤Research的擔子。所以正如Felix所料，三月的Spring Break就是回港的日子，好讓我與太太及一眾親友聚聚。大既會在三月六日便抵港，電話無變，見字請速聯絡 :-)

The Icon A5 - Sport plane?

Doesn't it look like a sport car? This little plane can go up to 120mph and requires only a 20-hr sport pilot training, it's going to turn the aviation of mankind to a new page.

A Little Gift Box

閒記就是這樣容易令人忘記。筆者忘記去寫，讀者忘記去看。

今天收到太太寄來的小禮物，自不然就想起要「update」這個「龜 blog」。因為這幾天氣溫已降至近乎零度，本想關了外門的小窗，卻竟發現一個小包裹就在門與門之間靜待著，可說是雪中送碳。

想不到一轉眼又回來了美國一個半月，踏入PHD的第四年，要是你不是一個想「hea」的人，總也會覺得壓力及工作都大加，實是不容易過的日子。做PHD或是說做學問的，總算是會有點抱負吧！可以的話，莫論會否投身學術界，也倒想有一點成績或貢獻，如此說來，壓力就是難免的，希望畢業的時候能夠有五份「first author」的文獻，而有一份可達「impact factor」20 的就好了，當然這個是「best case scenario」，但唯有就是盡力而為，無愧於支持我的人！
話又說回那小包裹，內有很多香港特色東西，有玩的，有賞的，有熱氣的，也有清熱氣的，可算是頗有心思。而值得一提的，莫過於森姆與Cathy的遊戲碟，好為沉悶的學習增加點點色彩，多謝熊生熊太同熊女！說到家人及一些老朋友，總令我想起香港的萬分好。
無論如何，盡快畢業才是最實際！

ISMB 2008 Toronto

Just came back from the ISMB (Intelligent Systems for Molecular Biology) 2008 conference at Toronto! It was a 5-day conference from 19th to 23rd. Due to the 'expensive' registration fee (550 at least for early bird), we chose to just drive from New Haven to save cost. Originally I thought an 8hr or more drive would be very exhausting, but it turned out the road trip was not that bad and was kind of fun. I guess it might not be too much worse than flying considering all the waiting and connecting time. So we (I, Mohamed, Pavi, and ThaiBinh) drove to Toronto on 19th in the morning and arrived at 8:30pm. We stopped by the Niagara Falls on the US side and visited briefly. If it was not raining, we would have spent a longer time and took a boat trip there. But it's not a problem since there is always next time : ) We spent most of our time (relatively) on the conference so we haven't really explored Toronto that much. But as usual, there are always talks that you can skip : ) So in the afternoon before the day we left, I bought a one-day pass and did a super quick sightseeing of Toronto. I took the Metro subway to the Queen's Park, University of Toronto, Royal Ontario Museum, Casa Loma (some sort of castle), and then took the street car to the Lake Ontario and back to our Hotel on King street. My overall experience of Toronto is that people are in general quite nice. The subway is clean and convenient. The city is also quite organized. The bad thing is that the QEW always seems to have traffic and the conference didn't have enough food and water provided, ridiculously. Besides, we were also invited by Meisha to have a get together at her home on Sunday and enjoyed a very nice treat from her whole family. And also we got a chance to meet with Pavi's mum as she is now working in Toronto. Her mum was so nice that even treated us a lunch at the Richtree restaurant : ) On our way back, we visited Rochester (Mohamed's feel-like home) and RIT, and almost tried 'something different' for our dinner. And finally, under the quite severe storm, we safely came back around 2 in the morning!

Photos: http://picasaweb.google.com/hugolam/ISMB2008Toronto

MS Graduation

On May 26, 2008, we, the CBB 3rd year students, walked at graduation all together and took our MS degree en route to PhD. It was such a fun and memorial moment not only because we walked together with the presence of our families, but also because we witnessed the conferral of the honorary doctoral degrees to Paul McCartney and Cesar Pelli at the same time! P.S. it was the first graduation ceremony that I attended!

Mac OS X

After my IBM (Lenovo) T60 died with a couple of hardware problems, I got a MacBook Pro as a replacement. When I was using Windows, I had a perception that Mac is a legend in the OS field as its stability and usability are so well received. Considering they build the OS and the machine, plus the OS is Unix based, it still makes sense to have such a reputation of performance. Honestly, I was quite happy with my Mac in the first week and with no doubt its usability is so much better than Vista, which I think unnecessarily imitated many of the Mac UIs that don't fit very well into their realm. As a user that extensively uses Linux daily, I feel more convenient using Mac with its built-in terminal, ssh, sftp, vnc, and virtual desktop (spaces). And most admirably, it comes with Java out of the box. That's everything I need. I would be really pleased if it can truly maintain its stability, at least for longer. As an IT professional, I wouldn't blame the OS because of individual program crashes. As in the past years I had never thought Windows was really that bad, considering it runs on a large variety of machines, until Vista came into play. I would say Windows 2000 is so far the best version of Windows I have ever used and Vista, in my opinion, is somewhat comparable with Windows Me, sadly. No matter what, the bottom line is that in my theory, an OS that is claimed to be good shouldn't in any case crash just because of an individual program crashed. Unfortunately, my Mac crashed twice in two weeks so far just because of individual program problems, not to mention some other minor bugs that are well discussed in the forums but are still outstanding. I originally thought it could be some sort of memory problem. However, the best memory tester for Mac, MemTest, said they are good. Although I am sure many people would have never encountered such an experience with Mac, nor they would have been aware of it, if it does happen and my Mac OS is genuine, I am a little bit reserved in its legendary stability, at least with that of Leopard.