TC_Chu's Point

What is Bioinformatics?

Let’s assume we have a species of bacteria that is part of the normal millions of ‘good’ bacteria living on and inside healthy human beings; we’ll call this Bacteria X.0. One day Bacteria X started making people very ill. What happened to Bacteria X.0 to make it become the harmful Bacteria X.1? Let’s see how we could answer this question using bioinformatics, along the way gaining insight into the wonderful world of bioinformatics.

Using traditional molecular biology techniques, we isolate Bacteria X and extract its DNA. Then we “sequence” this DNA. Cue the first link in the bioinformatics chain: acquiring data! Acquiring data is the process of generating useable data from a biological sample. In our case, deriving and determining the DNA sequence of the Bacteria X genome.

The next link in the chain is storing this sequence data. While bacterial genomes are typically small, other genomes, such as those of human beings, can produce terabytes (1000 gigabytes) of data.

Now we analyze this sequence data. There are people who specialize in developing computational tools to analyze and visualize data, versus people who actually analyze the information. A typical analysis for our sample case might be to first graphically visualize and compare the genome of the original, harmless Bacteria X.0 with the genome of the new, harmful Bacteria X.1. A scientist might observe a segment of DNA in Bacteria X.1 which is not present in the original Bacteria X.0. This new region of DNA may be responsible for the harmful effects, so the next analysis steps might be to drill down deeper into this region and see what genes lie there, what the function of those genes are, where they may have come from, etc.

[Remember: all assumptions made and conclusions drawn in this example are hypothetical and for illustrative purposes only.]

In this example, we encountered at least 4 different specialized areas within the field of bioinformatics:

1)      Acquiring of data (working with machines and equipment, sequencing DNA)
2)      Storing data (typically working with databases)
3)      Developing tools to analyze and visualize data (programming)
4)      Analyzing data (statistics, analysis)

Typically, individuals will specialize in one particular area rather than working simultaneously across all these fields. That, combined with all the different applications of bioinformatics, means you could ask 100 different “bioinformaticians” what they do and get 100 very different answers!

 

Breaking the Genome Bottleneck

The group plans to sell its so-called "Bina Box" preloaded with software that can reduce the 300 gigabytes or so of raw data from a human genome into a few hundred megabytes of genetic information. The box will upload the compressed dataset to Bina's cloud service for storage, sharing, and further analysis. The Bina Box can do the initial heavy lifting and make the data small enough to send to the cloud, the company says.

Bina Technologies says its system does this initial processing of genomic data at speeds that are orders of magnitude faster than tools made available by the Broad Institute, the MIT-Harvard joint genome center. What takes about a week using the Broad's genome variation analysis pipeline on a high-end eight-core machine on Amazon's cloud can be done in about two hours on a Bina Box, says Bani Asadi. The company expects to publish a full description of its comparison to other analysis pipelines in the coming months.

via MIT Technology Review

 

Bases to Bytes Cheap sequencing technology is flooding the world with genomic data. Can we handle the deluge?

The cost of sequencing human genomes is plunging—in the most advanced genomics centers, it's falling five times faster than the cost of computing. Increasingly, people are getting their DNA sequenced by companies and research labs in a search for clues about genetic variation and disease.

But the industry must figure out how to cheaply store all the resulting data. Each of the 3.2 billion DNA base pairs in a human genome can be encoded by two bits—800 megabytes for the entire genome. But considerable data about each base is usually collected, and genes are often sequenced many times to ensure accuracy, so it's common to save around 100 gigabytes when sequencing a human genome with a machine made by industry leader Illumina. Keeping this much data about every person on the planet would require about as much digital storage as was available in the whole world in 2010.

The trick, then, will be to save less. Harvard geneticist George Church says that eventually only the differences between a newly sequenced genome and a reference genome will need to be stored. That information could be encoded in as little as four megabytes. Then your genome might be just another e-mail attachment.

via MIT Technology Review

 

DNA: The Secret of Life

via Amazon

前半段關於基因改造食物的部份差點看不下去 就算那是James D. Watson說的 後面有關基因治療的部份 我也是不是很同意 （我支持體細胞（Somatic Cell)基因治療 而不支持性細胞（Germline Cell)基因治療）因為如果你知道目前把好的基因植入你的細胞是使用反轉錄病毒而且你完全不知道會把基因植到哪邊 光是這一點就讓人不放心（對於重大的基因疾病這是兩難的選擇）Watson對基因工程的看法太過天真了 但是我同意我門應該對基因做更多的研究 甚至於找出與行為相關的基因 不是要逃避責任而是知道有這樣的缺陷才能用適當的教育或是環境來改善

關於基因改造食物 (1)

如果孟山都(Monsanto)公司覺得自己的產品是那麼的值得驕傲 請在每一件使用貴公司的種子而生產的食物與沿生食品上打打上 ”Monsnto Indside" 不是很棒的一件事嗎？ 學學人家Intel and Windows 在每一臺電腦上都貼上亮晶晶的貼紙 不是很光榮的事嗎？

讀完“欺騙的種子”有感

Why a Portable DNA Device Could Yield Better Data

The technology relies on the fact that a DNA base, or a combination of bases on a DNA strand creates a characteristic disruption in a current as it passes through the nanopore. Electrodes measure the change in current flow as DNA molecules are fed through protein nanopores; an electrical gradient drives the DNA through the pore, while molecular "controllers" attached to the molecules mechanically slow them down so that their electrical signals may be recorded.

This approach has two important advantages.

First, the system is compact and doesn't require a supply of expensive reagents. That means sequencing can come out of the lab, making it useful for personalized medicine or for use in resource-poor clinics. Indeed, the disposable sequencer the company is about to introduce is the size of a USB memory stick.

Second, the technology reads much longer stretches of DNA than other rapid sequencing approaches, which means it has the potential to be better at spotting important "structural variants" related to disease. These variants occur when a whole segment of chromosome is moved, inverted, duplicated, or otherwise changed. When DNA is chopped into shorter stretches to be sequenced and then put back together on a computer, it is easier to miss, or misinterpret, such variants.

via Technology Review

synthesis.cc 

Device Brings $1,000 Genome Within Reach

At $149,000, the new machine is about three times the price of the Personal Genome Machine, the sequencer that the company debuted about a year ago. But the DNA-reading chip inside it is 1,000 times more powerful, according to Rothberg, allowing the device to sequence an entire human genome in a day for $1,000—a price the biotech industry has been working toward for years because it would bring the cost down to the level of a medical test.

via MIT Technology Review

 

Find Your Inner Neanderthal

In the last few years, scientists have uncovered clues not just to what the lives of Neanderthals may have been like, but also clues that tell us more about what it means to be a modern human.

Most interesting of all is that, although Neanderthals disappeared long ago, their DNA lives on in all non-African people.

http://spittoon.23andme.com/2011/12/15/find-your-inner-neanderthal/

PS.我在網路上的看過那個分析資料 蠻有趣的 因為收集到的尼安德塔人的基因量真的很少 如何分析這些資料和方法很有趣 (沒記錯的話是MIT Bioinformatics的課　一個很cool的年輕教授）

 

 

Is Autoimmunity a Result of Genetic Adaptation to Pathogens?

Although about 95% of the observed human genetic diversity appeared to be due to non-selective processes, a finding that was not surprising, adaptation to local environments—and specifically to pathogens—also accounted for a significant amount of genetic diversity. Viruses, bacteria, protozoan organisms that cause malaria and leishmaniasis, and parasitic worms are all examples of pathogens.

The study’s findings suggest that about 100 human genes have been strongly influenced by pathogenic organisms. Parasitic worms seem to have posed the most pressure on human genes. Because worms are complex organisms with longer lifespans than more simple pathogens, they may have co-evolved with people and exerted more pressure on the human genome.

...

This study offers new evidence for the hygiene hypothesis, a currently unproven theory suggesting that ramped up immune systems originally evolved to protect people from infectious organisms. As societies devised ways to keep pathogens at bay, however, their immune systems failed to adjust and they began to suffer from immune diseases characterized by too much inflammation.

http://spittoon.23andme.com/2011/11/30/is-autoimmunity-a-result-of-genetic-adaptation-to-pathogens/

 

Epigentics

If Gene is the program,regulation is condition block and epigentic is condition compilation . A programmer's point of view.

I think the early development enviroment has more impact on after birth enviroment impact on epigenitics and regulation control. Also the stem cell to normal cell creation enviroment is a key. I think these microenviroment has a lot more impact on living enviroment .

And I also think , we are still living in RNA world. I belived there are a lot to discovery inside the nucleous. There are must some kind of DNA house keeping job maintain by RNA. Like chaperone protien help protien folding.

Some though after read "The dynamic genome, A general introduction"

Last Update – 18 August 2011 (Biopython 1.58)

http://biopython.org/DIST/docs/tutorial/Tutorial.html

http://news.open-bio.org/news/2011/10/chromosome-diagrams-in-biopython/

Transcriptome

The transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells.

http://en.wikipedia.org/wiki/Transcriptome

'Junk DNA' defines differences between humans and chimps

The research team lead by Georgia Tech Professor of Biology John McDonald has verified that while the DNA sequence of genes between humans and chimpanzees is nearly identical, there are large genomic "gaps" in areas adjacent to genes that can affect the extent to which genes are "turned on" and "turned off." The research shows that these genomic "gaps" between the two species are predominantly due to the insertion or deletion (INDEL) of viral-like sequences called retrotransposons that are known to comprise about half of the genomes of both species. The findings are reported in the most recent issue of the online, open-access journal Mobile DNA.

"These genetic gaps have primarily been caused by the activity of retroviral-like transposable element sequences," said McDonald. "Transposable elements were once considered 'junk DNA' with little or no function. Now it appears that they may be one of the major reasons why we are so different from chimpanzees."

via http://kevin-gattaca.blogspot.com

What European DNA Can Say About Ancestry, Disease Risk, and Cultural Traits

All the drama in the European Union right now — the debt crisis, the North-South divide and the kvetching over the wisdom of a common currency — has reignited talk about the cultural divide between people on the continent.

But is the divide more than a political and cultural one? Is there a deeper difference among the people of Europe or those of European ancestry than whether Germans have a firmer handshake or are more punctual, or which nationality prefers a kielbasa to köttbulla?

There may be, and those differences can be seen in people’s DNA.

Although all humans are over 99 percent identical genetically, even in the tight geographic confines of Europe there is enough genetic variation that 23andMe researchers can use it to determine from where in Europe a person, or a person’s ancestors, came.

http://spittoon.23andme.com/2011/10/21/genes-and-geography/

Genetic Variation Influences How We Respond to Reinforcement

A study published this month suggests that rs1799971 also influences learning through positive reinforcement. The researchers behind this study tested if individuals with different versions of rs1799971 were more or less likely to continue choosing the right answer in a video game if they received reinforcement (in the form of a small cash prize) for correct answers.

The authors found that positive reinforcement prompted individuals with the AA genotype at rs1799971 to continue to choose the right answer over time. That is, positive reinforcement motivated these individuals to learn. In contrast, individuals with at least one copy of the G version at rs1799971 (AG or GG) were less motivated by positive feedback—these participants did not continue to choose the right answer over time.

http://spittoon.23andme.com/2011/09/20/snpwatch-genetic-variation-influences-how-we-respond-to-reinforcement/

看來吃軟不吃硬或是軟硬都不吃是一種遺傳!

Gamers solve decade-long simian AIDS protein conundrum

For over a decade, researchers have been arduously attempting to reconstruct the folded shape of M-PMV with the aid of the task-specific Rosetta software, but to no avail. Now, in what they're calling a possible first, gamers were able to do what scientific brains and algorithms could not, creating a sufficient model for molecular replacement -- all in just three weeks. Feel like dedicating your leisure hours to this worthwhile cause? Then be sure to hit up the source link below, and transform yourself from couch potato to couch crusader.

via Engadget

把蛋白質折疊當成Game來玩 請Game玩家來解決科學家一直找不出來的方法 (玩家們只花了3星期 兒科學家花了10年)

http://fold.it/portal/

An RNA Switch for Stem Cells

Mitchell Guttman, first author of the study and a graduate student at MIT and the Broad Institute, says that when the Broad team discovered more than 3,500 unique lincRNAs in the human and mouse genomes in 2009, "the potential was enormous, and we wanted to know what they could be doing."

To answer that question, the researchers focused on understanding lincRNAs' role in embryonic stem cells. Using a technique called RNA interference, they systematically shut down the function of each of more than 200 lincRNAs previously identified as playing a role in embryonic stem cells. They then profiled the genes expressed in the cells and studied their functions. They found that most lincRNAs have widespread effects on cells, and that they help control the fate of stem cells. The team identified about two dozen lincRNAs that help maintain the cell's pluripotency—its ability to beget all other kinds of cells—and a similar number of lincRNAs that repress genes involved in differentiating into other cell types.

via MIT Technology Review

Learn R Quickly !

If you currently use another statistical package, why learn R?

1. It's free! If you are a teacher or a student, the benefits are obvious.
2. It runs on a variety of platforms including Windows, Unix and MacOS.
3. It provides an unparalleled platform for programming new statistical methods in an easy and straightforward manner.
4. It contains advanced statistical routines not yet available in other packages.
5. It has state-of-the-art graphics capabilities.

http://www.statmethods.net/

不錯的R學習網站 書也不錯 很實用

23andMe Offers Free Genetic Tests to African Americans

To date, research into the genetic cause of disease has been overwhelmingly white.

Of the participants in the most common type of genetic disease study, 96 percent are of European descent. Growing evidence suggests that the results of these studies, which encompass hundreds of thousands of people, may be less relevant or even irrelevant to those in other ethnic groups.

23andMe, a direct-to-consumer genetic testing company, aims to shift the balance. It will offer free testing to 10,000 African-Americans as part of a research initiative to expand the diversity of its genetic database. The company hopes the project, announced last week at the National Urban League conference in Boston, will shed light on the genetic basis of disease in this population. More than 1,000 people have signed up on the website in the week since the project was announced.

via MIT Technology Review

RStudio available at cloudnumbers.com

RStudio™ is an integrated development environment (IDE) for the statistical software R (www.r-project.org). It combines an intuitive user interface with powerful coding tools to help you get the most out of R.

cloudnumbers.com provides researchers and companies with the access to resources to perform high performance calculations in the cloud. One often used application at cloudnumbers.com’s computer clusters in the cloud is the statistical software R.

via R-Blogger

Massive Project to Study the Link between Genetics and Health

Now Kaiser Permanente, the nation's largest nonprofit health plan, has announced that it's finished the first phase of a massive project to compile genetic, medical, and environmental information for 100,000 of its members. Researchers also analyzed the length of participants' telomeres—a molecule structure at the tip of the chromosome that has been linked to aging. This represents the largest telomere study to date.

The resulting data, gathered in collaboration with the University of California, San Francisco, will soon be available to outside researchers who study how different genetic and environmental factors influence disease. It took about 15 months for the team to collect and analyze the genomes of 100,000 people ranging in age from 18 to 107. The team used gene microarrays—small chips designed to quickly detect hundreds of thousands of genetic variations across the genome.

via MIT Technology Review

Microarray Bioinformatics

很不錯的書 左手說明Microarray 右手說明資料分析的方法 最後再教你有關實驗的設計

via Amazon

The Search for E. coli Gains Speed

Bean sprouts were briefly added to the list of foods seen as potential sources of E. coli 0104—a new strain that has infected more than 2,300 people and killed 23 in Germany over the past three weeks. The list of potentially dangerous foods includes cucumbers, lettuce, tomatoes, and other raw salad vegetables.

The rapid reprieve for sprouts can be attributed to the availability of high-speed pathogen-specific tests. These assays, laboratory procedures that measure the biochemical activities of food samples, can now return reliable results in as little as 10 to 24 hours.

"As soon as we finished sequencing the DNA of this strain, we made the results public, like any ethical company would," says Nir Nimrodi, head of food safety at Life Technologies, which has developed a custom test for E. coli 0104.

via MIT Technology Review

Simpler Genome Sequencing

A Massachusetts startup called Noblegen is developing a simplified version of nanopore genome-sequencing technology—a technique that promises high speed and low costs but that usually requires complex instruments to carry out. Noblegen, founded last spring, says its technology's ability to directly and rapidly read DNA sequences could make it economically feasible to bring sequencing technology into clinical labs to diagnose cancer and other diseases.

Noblegen CEO Frank Feist says the company's goal is to sequence at a rate of 50 bases per second. The company won't divulge details of its current prototypes, but says the technology could be scaled up to arrays of 400 by 400 nanopores that sequence over 500 gigabases an hour—or about 30 genomes in 15 minutes.

via MIT TEchnology Review

PS.Bioinformatics 將會越來越好玩了!

Exome sequencing

 

Exome sequencing (also known as targeted exome capture) is an efficient strategy to selectively sequence the coding regions of the human genome to identify novel genes associated with rare and common disorders.^[1] Routine whole genome sequencing of large numbers of individuals is still not feasible partly due to the high cost associated with the technique. At present, it is necessary to use an alternative approach, in which certain regions of the genome, such as the “exome”, are targeted, enriched and sequenced, which requires ~5% as much sequencing as a whole genome.^[2] The “exome” represents all the exons in the human genome (i.e., the transcribed region of the genome). Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein and untranslated region flanking them (UTR). UTRs are usually not included in exome studies. In total there are about 180,000 exons found in the human genome. These protein coding regions constitute about 1% of the human genome which translates to about 30 megabases (Mb) in length.^[2] It is estimated that the protein coding regions of the human genome constitute about 85% of the disease-causing mutations.^[3]

http://en.wikipedia.org/wiki/Exome_sequencing

 

 

R-Tutorial

Welcome to R Tutorial. We provide an introduction to the R programming language, and illustrate its use by solving elementary statistics textbook exercises. Beyond the basics, we also cover topics of GPU computing in R. Hope you find the material helpful, and this site serves the intended purpose of being a stepping stone for further study.

http://www.r-tutor.com/

A good place to learn R

Bioconductor

http://bioconductor.org/

以R為開發環境的opensource bioinformation tool kit

HMMER3: a new generation of sequence homology search software

HMMER is used for searching sequence databases for homologs of protein sequences, and for making protein sequence alignments. It implements methods using probabilistic models called profile hidden Markov models (profile HMMs).

Compared to BLAST, FASTA, and other sequence alignment and database search tools based on older scoring methodology, HMMER aims to be significantly more accurate and more able to detect remote homologs because of the strength of its underlying mathematical models. In the past, this strength came at significant computational expense, but in the new HMMER3 project, HMMER is now essentially as fast as BLAST.

http://hmmer.janelia.org/

Other Resouce

http://www.bioinformatics.org/wiki/Hidden_Markov_Model

http://www.hiddenmarkovmodels.com/index.html

Computational Genome Analysis: An Introduction (Statistics for Biology and Health)

我覺得這本書在介紹Bioinformation深入淺出 由簡而繁 還有一些R 的範例 對於不是學生物的人來說很適合