What is bioinformatics?

It can simply be defined as a link between biology and computer science, in which the biological data is processed and computed through software, to yield an output, that is later interpreted in different ways.

Biological data indicates the nucleic acid or protein sequences, their simple or complicated forms, whereas the software is the computer program, specially designed for processing these data in a certain way, done using a certain algorithm (it is a recipe to solve a program problem). The data output is usually numerical or visual (often graphical), but mostly it needs to be well understood. The last one is the key point in the bioinformatics.

What is the need of bioinformatics?

In the research field, we need to be led to certain road, to choose one way or another, or to try many options until we define our research plan. Bioinformatics simply brings the solutions into your hands by a few mouse clicks.

One simple example to make it all clear is the PCR (Polymerase Chain Reaction). We always need to design a primer to trigger our reaction. If we did this through the ordinary ways, we would have to practically try out so many primers and this would surely take a tremendous amount of time. Now, what if you are computer- and internet-literate? You can simply use software to get many primer options for the DNA piece under investigation; doesn’t this save time, efforts and money?

Can bioinformatics be useful in different ways, other than the PCR example?

Some people may think that using bioinformatics is limited to some fields of biological research, and some others might think it is only a matter of prediction, which always needs to be evaluated for its accuracy, specificity and efficiency. But indeed, bioinformatics can be used in the analysis of nucleic acids and proteins.

Analysis?!! That is a vague word, how can you analyze a protein using bioinformatics?

Now you’ll see what bioinformatics can do for protein analysis:

1. Retrieving protein sequences from different databases, either specialized or general databases and it is not an easy job if you would think so.
2. Computing a protein or amino acid sequence to obtain:

• So much of the physicochemical properties of you sequence like the molecular weight, and isoelectric point…etc
• Hydrophilicity / hydrophobicity ratio

Both of the above can provide us with the probabilities of one protein acting as a receptor on the cell surface or it might be antigenic or even secreted outside the cell.

3. On the prediction aspect, we can predict:

• Some sequences of certain importance, e.g. the prediction of signal peptides that can lead us to know the secretory proteins of one organism
• 2ry structure of your protein
• 3ry structure of your protein

The last two points are applications of what is called structural bioinformatics, through which computer is capable of predicting the 2ry and 3ry (3-D) configuration of your protein, using special programs with advanced algorithms and artificial intelligence. Amazingly, this may be useful in understanding the receptor-substrate interactions.

4. Comparing sequences to obtain the best alignment (it means compare 2 or more sequences to find their relation to each other, i.e. finding similarities and differences), it will help in:

• Classifying your protein and relate it to its protein family
• Making your evolutional expectations about your protein to define whether it descends from another protein or not. This is called phylogenetic analysis, at which the proteins under investigation are studied to know which protein is considered a mother to the others, which are the daughter, the grand daughter, and so on
• Detection of the common domains, this will help us understanding the functions of unknown protein when it is compared to sequences of other proteins of known functions

Then, what will we gain if we compute DNA? Or you can say, what can bioinformatics do for DNA research?

On the same level as with protein, though different applications, we can use it in:

• Retrieving DNA sequences from different databases
• Computing a sequence to obtain information about its properties (like proteins) e.g. GC% which could be used with other properties to identify a gene
• Assembling sequence fragments (usually DNA is sequenced in the form of fragments which are needed to be assembled in the best way, bioinfo. does this in a faster and more accurate way rather than the ordinary assembly)
• Designing a PCR primer
• Prediction of DNA and RNA secondary structures (e.g. prediction the stems and loops of the t-RNA)
• Performing alignments between 2 or more sequences that can lead to many applications (as those mentioned above in protein alignments)
• Finding of repeats, restriction sites, Single Nucleotide Polymorphism (SNPs), and/or open reading frames, all of which have so huge applications in the medical and paramedical fields and typically in the research activities.

Tags: algorithms, alignment, analysis, artificial intelligence, Bioinformatics, biology, computer science, DNA, PCR, phylogenetic, phylogenetic analysis, protein, RNA, sequence, signal peptide, single nucleotide polymorphism, SNPs

Meeting a scientist is like reading many books in few minutes, books of science and books of life. To me, though, meeting Dr. Niyaz Ahmed ⁽¹⁾ was like reading a library. He is one of the most active advocates for Open Access (OA) and open evaluation of science. His support for OA is not just by words, but through sharing effectively in such purpose as he is a section editor of Microbiology and Genomics in PLoS ONE and a chief editor in Gut pathogen, the official journal of ISOGEM (the International Society for Genomic and Evolutionary Microbiology), in Sassari, Italy, of which Dr. Ahmed is a co-founder and the General Secretary. ISOGEM members work on developing post-genomic ideas to serve the public health and the environment. Dr. Ahmed is one of the faculty members of Faculty of 1000 Biology, the expert guide to the most important advances in biology.

Dr. N. Ahmed’s early start was in India as he graduated in Veterinary Medicine and obtained his Masters degree in Animal Biotechnology, then his PhD in Molecular Medicine. Currently, he is also based in India, in Hyderabad University as an Associate Professor of Biotechnology and a staff scientist in the Center of DNA Fingerprinting and Diagnostics in Hyderabad. This is not everything about him, his homepage reveals more, especially those pioneer achievements in the research world in India, like being a co-principal investigator of the Mycobacterium W genome program, India’s first whole genome sequencing project, and the most amazing part of his research is working on Helicobacter pylori chronological evolution and phylogeographic analysis.

Having read about all these achievements, I had many questions in mind, but, knowing how busy he is,  I tried to reduce them to the following few questions that cover different areas of his activities.  Dr. Ahmed generously agreed to answer them all.

Dr. Niyaz Ahmed, any microbiologist would be honored to meet you, and so am I. I am one of the “Micro Writers” blog members; we are young enthusiastic students from Faculty of Pharmacy, Cairo University in Egypt, mostly undergraduate and some graduate students, who are looking from the blog window towards the research world. Most of us wished someday to become scientists; “Micro Writers” is like the first real step on the right way. Our blog focuses on different areas of microbiology. It is like a message by students so far from Egypt, but hopefully from other places as well, to students all over the world. I read a lot about your achievements, especially those concerning the H. pylori phylogeographic analysis. As you have a great experience in research, reviewing articles and especially because you own a blog, I would like to ask you a few questions, and get them published with your answers on the blog, in order to teach and guide not only us, but the all students from everywhere.

• N.A.: I am very much enthused by your offer and would like to be interviewed at Micro-Writers blog. Please let me know your questions and I would try to answer them all.

Since you are working on the population structure of H. pylori, and on their chronological evolution, can the phylogeographic analysis of bacterial strains lead to infection control or innovative treatment? If yes, how?

• N.A: It may not directly lead to product development as such, but, it can definitely explain how the spread-patterns of this organism are? and that has a lot of bearing on infection control in terms of tracking the infection sources. Also, knowing separate lineages in greater details offers accurate diagnostic development which in turn helps keep a tab on their emergence or otherwise.

If phylogeographic analysis can teach us about migration of some strains from one place to another, can we use it in a reverse way? I mean can we use this analysis to learn about the origin of mankind, and his migration routes?

• N.A.: Indeed, we can do that. For a bacterial parasite to become a surrogate marker of human history (including migrations), it needs that its population structure mimics with that of the host. It is now established that H. pylori has most probably coevolved with its human host and thus its population structure is juxtapose to the human population structure. Therefore, we can use it as a marker of human history and geography.

Concerning the unpublished ideas of your studies, which suggest that bacterial proteins may be able to perform both the immune stimulatory and immune evasion tasks, the simple question is, do you think bacteria are smart? Do they have that smart controlling machinery that is able to distinguish between all these factors?

• N.A.: The term ‘smart’ is reserved for humans. However, we can say that bacteria are highly adaptable. Several bacterial traits such as quorum sensing, community interactions (such as that seen in biofilm formation), molecular mimicry, immune evasion, dormancy etc. definitely point towards their being ‘intelligent’.

You talked about the host-pathogen relationship. I would like to add one more suggestion, which is that bacteria may face the immune system or the host body as a community of workers, not as independent cells. It is like the idea of sociomicrobiology in biofilms. Does this social behavior apply to other communities of bacteria other than bioflims, e.g. the community of H. pylori cells against the human defense system in the stomach?

• N.A.: Indeed there is a body of evidence coming in via both in vitro and in vivo observations that H. pylori cells tend to form biofilms which is favored by gastric mucin and by mutations of luxS, and the cagE type IV secretion gene. This observation is important to understand H. pylori’s resistance to host immune responses and antibiotics, and in microenvironmental pH homeostasis which conditions and streamlines the growth and survival of H. pylori in vivo.

You mentioned at your homepage that strains of H. pylori in the Southern Asia are not life-threatening in the same time they may cause gastric cancer in the West. Do you think the lifestyle in Southern Asia, especially the food (extra-spicy food), might lead to evolution of these non-lethal strains, and vice versa in case of the western lifestyle?

• N.A.: It is observed that high incidence of H. pylori in India (nearly 98%) does not positively correlate with the rates of invasive outcomes and life-threatening consequences of the infection (cancer). It is possible that the food that is eaten here (rich is herbs and vegetables) has some protective advantage in terms of governing the micro-environmental conditions at the niches colonized by H. pylori. Another aspect is genetic susceptibility or resistance to gastric cancer which is to be considered as well.

Adoption of open access (OA) in science, isn’t it a huge responsibility, with great challenges, most probably the funding challenge? I mean, who will pay always for open access science?

• N.A.: Open Access is a reality and the most practical approach to augment knowledge sharing towards science education, research and the practice of medicine and agriculture. Developing countries that have brains but no library budgets and that have been until now deprived of access to knowledge will be at a great benefit with this OA revolution. I do not see any challenge here as funding agencies such as NIH, Howard-Hughes Institute and Welcome Trust have already started subsidizing costs for OA in a big headway.

You started in India; did you feel some bias (in the international journal publishing) towards some western countries (e.g., USA, Germany, France, UK, etc.)? Do you think that the researchers from the developing countries should be encouraged in a way or another, especially against the fees and restrictions of publishing?

• N.A.: I firmly believe that originality and novelty have no barriers. If your ideas are novel and your findings well defended, no one can stop them from seeing light of the day. Developing country scientists are equally respected – I can cite my own example, I was made Section Editor at PLoS ONE to oversee an extremely important area, microbial genomics; for this appointment, my affiliation and my geographical co-ordinates were not the important criteria but my standing in the field of medical microbiology, the efficiency with which I handled the issues and my professional commitment to the cause and ethos of OA publishing. However, there may be exceptions of which I have no idea. Nevertheless, this is a free world and if one has zeal and dedication, success is not that far. These days, publication restrictions based on novelty or being on ‘cutting edge’ or otherwise, are no issues. Developing country scientists are thus free to bring forward their research even on topics which may not be interesting to a few ‘glamour magazines’ of science, but they are welcome at descent venues such as PLoS ONE; they are free to even send in aspects of their folklore medicine, their local environmental problems, cropping, local biodiversity, energy production, their cultural and human anthropological aspects (and topics cutting across these) wherein no one is their competitor! Fees for publication is not a problem, PLoS and Biomed Central both waive off publication charges quite generously in almost all cases of genuine inability to pay.

In an old interview, you said that blogs are a good chance for young scientists to express their ideas for free, what about the older scientists in the developing countries who need more space to express their research activities, in the same time so many restrictions are imposed on them to get their papers published in the international journals?

• N.A.: Old, and young, all need to be part of the dialogue. Even for busy academics, blogs are extremely helpful although they are no alternative to a proper publication of results or viewpoints. Blogs can effectively blend zeal and enthusiasm of ‘young Turks’ with the experience and patient advice of the ‘old guards’. Academic institutions in the developing countries should support such portals wherein students and faculty discuss research to arrive on novel interpretations and provocative ideas in an interdisciplinary environment of learning and enabling.

As an editor and reviewer in so many journals, what is your advice to some young Egyptian researchers like us in the “Micro Writers” blog who work with the fewest capabilities and with minimal resources, to get our papers published in an easier way?

• N.A.: I love the Micro Writers Blog. You are the torch-bearers for all other undergraduate students in our countries of the developing world. My advice is try hard to deliver your best. Do not write on complaints – write about solutions! Do not present as Egyptian, or African, think globally, be a part of global community in the best interests of humanity, the environment and wellbeing of all creatures. I can quote from the Holy Qur’an: “Wallatheena Jaahadu Feena Lanahdiyannahum subulana” (The more you dedicate yourself and strive hard, the more will be the opportunities and paths widened for you from the Almighty). (2)

 

Finally, I would like to thank you Dr. Niyaz for the time you gifted for us to answer my questions with plentiful ideas, objects, and words. I am quite sure, each one who reads this interview will get benefited more than once.

Dr Niyaz Ahmed (left) co-ordinating a ‘student-scientist-administration’ meeting with Nobel Laureate Prof. Peter C. Doherty (center) and Australian High Commissioner to India, Mr John McCarthy (right).

 

———

(1): Dr Niyaz Ahmed, PhD

General Secretary,  ISOGEM
Section Editor, PLoS ONE
Chief Editor, Gut Pathogens
Assoc. Editor, Ann Clin Microb Antimicrobials
Assoc. Editor, Acta Veterinaria Scandinavica
Faculty Member, Faculty of 1000 Biology
Corres. Fellow, Eur Helicobacter Study Group

 

(2): EL-Qur’an El-Karim, chapter #29 (El-Ankaboot), verse #69.

Image credits: Dr. Niyaz Ahmed.

 

Tags: Academic institutions in the developing countries, bacterial dormancy, biofilm, Biomed Central, cagE type IV secretion gene, chronological evolution, developing countries, Egyptian researchers, Faculty of 1000 biology, gastric cancer, gastric mucin, Gut pathogen, Helicobacter pylori, host-pathogen relationship, Howard-Hughes Institute, Hyderabad University, immune evasion, ISOGEM, luxS, microenvironmental pH homeostasis, NIH, Niyaz Ahmed, open access, phylogeographic analysis, PLoS ONE, quorum sensing, smart bacteria, the Center of DNA Fingerprinting and Diagnostics, Wellcome trust

If you try to search in the library or over the internet for AIDS, you will find a huge amount of information available. You will also figure out that all scientists reach a dead end at the step of treating or vaccinating against AIDS. Their stop makes you never stop thinking: why can’t they continue? Why is there no cure for such a disease? Or at least why can’t they stop the progress of this illness by simply making a vaccine? It is like reading the same book millions of times without understanding its end, then you re-read the last chapters but still “YOU CAN’T”!!

I think that we need to restart reading the book from its beginning. We need to re-read about the origin of AIDS infections, to know more about HIV genome, and how its genes function; then we may know how to slow down or terminate progression of the virus inside the human body or at least to stop its passage from an individual to another. Hence, we may be able to read the book again and this time we can understand its end.

AIDS was initially reported on June 5th, 1981. But, it is more precise to mention the first documented AIDS case, which was in 1959. At that time, no one was able to define such an illness; however, scientists did a favor for the humankind by preserving the infected tissues till someone would be able to define HIV, i.e. after 1981. I may ask why not before 1959? But who can answer a question like this?

The origin of AIDS has so many controversial theories, including conspiracy theories. One of these is that HIV arose as a result of leakage in the US governmental or military labs during the development of a biological weapon. You may ask Dr. Leonard G. Horowitz (the author of Emerging Viruses: AIDS & Ebola. Nature, Accident or Intentional? And Death in the Air: Globalism, Terrorism and Toxic Warfare) for evidence to prove such an idea. As wikipedia page of ” AIDS origins opposed to scientific consensus” mentions his theory which claims that AIDS virus was engineered by such U.S. Government defense contractors as Litton industries for the purposes of bio-warfare and “population control”.

Dr. Alan Cantwell (the author of AIDS and the Doctors of Death) supported this theory, by naming one scientist that led the US military research on homosexual and bisexual men between 1979 and 1981; he attributed these research activities to Dr. Wolf Szmuness. And, when Dr. Alan was asked about the cases that were reported before 1979, his answer was that the American media masked the truth at that time! This has been also mentioned on “AIDS origins opposed to scientific consensus” Wikipedia webpage.

Another unreliable hypothesis had been advanced by Edward Hooper, as he accused Hilary Koprowski, the polish virologist and immunologist who was preparing polio vaccine using tissue cultures from non-human primates during 1950s, that he might have transferred AIDS from monkeys to human. This idea couldn’t be evidenced when one of these vaccine vials had been checked in 2000 to show negative HIV or SIV (Simian immune-deficiency virus that infects chimpanzees). Also, by checking the protocols of that old research, it is clear they were working on monkeys’ kidney cells that cannot transmit AIDS. But can one negative vial become a prove for the whole negativity?!

The most accepted and recent theory assumes that HIV is an evolution from SIV. This Cameroon Chimpanzees theory was suggested in 2006 after a study on genetic samples from more than 1300 chimpanzees within 7 years by Dr. Beatrice Hahn. It seems that one person had been bitten by one of these apes or got cut while he or she was trying to slaughter one of these animals, maybe for eating purposes!!

If this Chimpanzee in the picture is the main suspect now for HIV triggering on earth, the question now is: Do we have current reports for the same transmission from apes to human? If yes or no, I think we need to re-study and search that SIV which might tell us something about its “daughter” HIV (as accepted by most of the scientists). It is like reading the book from its beginning not the last chapters, sure it will tell us new things.. Like what? I really dont know, it may be like the first idea that led to inventing the nuclear bomb, would you believe me if I told you more than 60 years ago that there is an idea to bombard the nucleus to make a huge bomb? It was just an idea, but the know how was not known. I think it is the same for the AIDS book: we need to re-read but we still don’t know what is going to happen after that reading. All I know that we need to re-read with a new vision, not the same ordinary way of reading.

Image credits: http://upload.wikimedia.org/wikipedia/commons/8/8d/South_Djoum_Chimp.jpg

Tags: AIDS, AIDS origin, Cameroon Chimpanzees hypothesis, Consiperasy Theories, conspiracy theories, Dr. Alan Cantwell, Dr. Beatrice Hahn, Dr. Leonard G. Horowitz, Dr. Wolf Szmuness, Edward Hooper, Hilary Koprowski, HIV, SIV