Thursday, March 12, 2015

SEQUENCING AND THE IDENTIFICATION OF VIRUSES FOR PUBLIC HEALTH (SCIENTIFIC)

BY CESAR PEREZ


One common problem in public health is the detection of pathogenic organisms, so it could be considered as a critical component in public health diagnosis. Thus, viruses detection and identification in clinical samples is always complicated. Traditionally, culture isolations and electron microscopy methods were used in order to find virus identity, but these common techniques have been replaced with PCR and other molecular tools. However, the problem with our attempts of identifying viruses  is that these don't present ubiquitous characteristics, similar to ribosomal DNA in organisms; consequently, there isn't  an universal protocol to diagnose and track viruses, and with the usage of different methods different viruses are described.
Svaraka and its team tried, in 2010, to propose a tool to diagnose viruses in clinical samples. They used metagenomic analysis in samples collected by EVS program in Netherlands, which goal was the detection of poliovirus circulation among Netherlands' hospitals. About the method suggested, metagenomics was amply used in the detection of different environmental samples , principally in the searching of Bacteria as pollution indicators or its ecological roles. The scientific team suggested this method due to its powerful detection of complete sequences from genomes of a sample, then it overcomes some limitations from other methods like too specificity in PCR (specific and global sequences that viruses don't present) and difficulties on isolation certain viruses.
Investigators found some interesting results. Firstly, it was suggested to use an method to separate viral fraction from all the sample because virus represents only a fraction from the microbial community and this analysis must be focused only in virus sequences. Secondly, sequences from different types of viruses were detected, from Enterovirus, detected with traditional methods, to new and scarce viruses at that moment like Saffold Viruses (SAFV). Third, complete sequences of all viruses, especially those which are new non-identified, were able to be related toward phylogeny to known viruses and make predictions such as if they are pathogenic or possibly pathogenic for humans. Finally, metagenomics provides large amounts of data which could be used on the study of proteins involved in the pathogenicity of certain viruses.
In conclusion, metagenomic is a powerful tool for virus detection in clinical samples. This method, could deal with the limitations in other molecular and traditional diagnosis techniques. Furthermore, the most notable implications is that sequencing technology is becoming more and more cheaper everyday, and it could be applied to distinct samples like feces, blood, cell cultures and more.
References
Svraka, S., Rosario, K., Duizer, E., van der Avoort, H., Breitbart, M., & Koopmans, M. (2010). Metagenomic sequencing for virus identification in a public-health setting. Journal of General Virology, 91(11), 2846-2856.

DIAGNOSIS AND PATIENT MANAGEMENT ARE CHANGING WITH NEXT GENERATION SEQUENCING (NON-SCIENTIFIC)

BY CESAR PEREZ


Next Generation Sequencing (NGS) technology allows to realize different types of analysis; among them we can inquire more and more inside the human genome, proteins, metabolism and diseases. Thus, the analysis of exome with high accuracy is possible nowadays. The exome is the portion of our genetic material, DNA, that is encoded to proteins which are going to enter into our metabolism, so the exome analysis is a powerful tool in health since it is direct related to development of the human body.
Dixon, alongside his team, performed a survey where the objective was to explore NGS's implications in public health, particularly exome sequencing. For its investigation, they focused on neuro-developmental disorders for various reasons. Firstly, neuro-developmental  disorders affects to 6% of the population approximately, and it has consequences on intellectual capability, epilepsy, autism, and muscular disorders. Secondly, these disorders are complicated to diagnose because it is difficult to get an neural tissue sample; consequently, almost 10.000$ per patient are spent in evaluations, and it represents up to 10% of the total US Center for Diseases Control's annual budget. Finally, health investigators observed that these diseases exhibit both clinical and genetic heterogeneity that makes them perfect for the use of certain genetic analysis.
In this project, investigators realized an whole exome sequence (WES) of 118 persons. In order to get the best representation of human population as they could, people with high levels of consanguinity were sampled, to increase the power of detection for some uncommon genes. Aditionally, they must have been diagnosed with a neuro-developmental problem or been related to some person with the disorder. The WES analysis provides some interesting results: common and obvious disorders could be diagnosed, a set of genes related to developmental abnormalities were discovered, and; in the rare case disorders, a pre-natal diagnosis possibly method was suggested. In contrast, WES is less accurate than it was expected due to incongruence on disorder's description, incomplete medical history, or non-clinical features present in patients possibly. Finally, the cost of the analysis was calculated between 2000$ and 4000$.
In summary, WES and other NGS technologies are important tools for diagnosis for neuro-developmental disorders, and rare case development problems in general. Although these technologies present some limitations, they represent a support to find disorders in human population. Furthermore, the greatest input of these new methods is the economic cost, 4000$ is greatly lesser than the amount that is spent in a single patient nowadays, and this value is tending to be less and less with the development of more powerful and trustable sequencing technology.
References
Dixon-Salazar, T. J., Silhavy, J. L., Udpa, N., Schroth, J., Bielas, S., Schaffer, A. E., ... & Gleeson, J. G. (2012). Exome sequencing can improve diagnosis and alter patient management. Science translational medicine, 4(138), 138ra78-138ra78.

RARE DESEASES IN SEQUENCING ERA (NON-SCIENTIFIC)

BY CESAR PEREZ


We know diseases capable of alter gene functionality, so they are changing people's good quality of life. Among all genetic diseases, many of them could be very rare in frequency inside human population, some anomalies are present on less than 200,000 persons in United States or 1 from 2,000 in Europe. Although low frequent health problems seem to be unusual, they affect millions and millions of people over all continents and countries. Thus, because of its frequency and difficult diagnosis, health care of a great number of people is insecure. However, genetic technologies and the knowledge on gene functions were rising and rising in our days, so this advances are going to be integrated to health and genetic disorders detection.
Before inquiring about diseases it is important to notice modern technology in genetic analysis. All organisms are composed by DNA as genetic material, at the same time, DNA is composed by four components: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C), so gene expression depends in a strong way on the combination of this four components. In order to understand DNA and reveal ATCG combinations, sequencing technique was developed, but it presents some limitations, the longer DNA is, the less accuracy on ATCG detection. In our days, sequencing accuracy is increasing due to the implementation of Next Generation Sequencing (NGS) technology. NGS avoids sequencing limitations analyzing millions and millions of short DNA fragments; this tool is universal for every biological entity, and its capacities are starting to be applied to human health.
With NGS came two new analysis: whole genome sequencing (WGS) and whole exome sequencing (WES). Both are powerful tools to detect genetic differences among people. WES is the most popular to detect different proteins in human body because it analyses only genes that becomes proteins in human body. However, the two techniques allowed scientists to detect genes such as those which are related to Freeman-Sheldon syndrome, Miller syndrome, and Schinzel-Giedion syndrome. In addition, there are projects that are implementing and improving different ways to discover more and more genes such as 1000 Genomes Project, Exome Variant Server, or HapMap Project.
Moreover, NGS based gene discovery revealed a lot of different sequences related to rare diseases, but the depth this problems  is still unclear. Nowadays, it is common to find rare diseases with relationship with others or discover new unrelated disorders. Anyway, NGS is a powerful diagnosis tool since it started to be applied in the study of inherit mutations or the frequency of a gene associated to a disease in a family. Finally, researchers are more excited with the applications of NGS technologies in public health since all the studies are deriving in the analysis of proteins or seeking for new ways in the development of diseases.
In conclusion, patients of rare genetic diseases are the most benefit with NGS revolution. From this point, the discovery of genetic variations among people will allow us to personalize medicine for each individual or each particular case. Furthermore, with the existence of The Human Variome Project, a database with all the genetic variations related to illnesses and health development, it is necessary an Human Phenome Project focused on create a database with the effects of this genetic variants on the human condition and healthy life.
References
Boycott, K. M., Vanstone, M. R., Bulman, D. E., & MacKenzie, A. E. (2013). Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nature Reviews Genetics, 14(10), 681-691.
Illumina. An introduction to Next-Generation Sequencing technology. Retrieved from: www.illumina.com/technology/sequencing_technology.ilmn on 16/02/2015.

Wednesday, March 4, 2015

Your DNA from spit (non-scientific)

Author: Eunice Lozada-Delgado 

It is known that to get your DNA (what gives you your identity in your cells) one only needs your spit. In fact, many companies have opted for this technique to provide services of ancestry and even to determine your susceptibility to getting a disease. This emerges from the idea that people nowadays are interested in their past ancestors as well as knowing beforehand the possibilities they have to acquiring a disease to maybe prevent it as much as possible. All this is possible thanks to the advances in genome technology where we can now even determine or “sequence” the whole genetic information or genome of one person. This we call genome is made up of your DNA which is made on four letters that repeated many times in mixed and different orders determine how you look like and your identity itself since no one else has the same order of the letters that you do in the whole world! Unless you have an identical twin duh. 

23 & me is a great example of a company that has provided this type of services of ancestry and determining susceptibility to obtain a disease to the general public. The way they develop the results is by asking the client to give a sample of spit through a kit they send them. With this spit sample they are able to sequence the genome (determine DNA sequence) but not completely, only by small strategic pieces called SNPs or single nucleotide polymorphisms. These are places in your DNA sequence where a single base pair (letter) is changed. So this is how obtaining a spit sample these people can actually identify you like CSI! To better understand this process view the video below:


By determining the identity of those specific SNPs in your spit sample they are able to compare it to their database and determine your ancestry as well as your probability of acquiring a disease related to those SNPs. This approach also has some ethical issues involved since not only will you receive these results but they will also keep them in their database. So even though they say that this is your private information, if somehow health insurance companies get their hands on those results (hackers exist) they can actually see your probability of acquiring expensive to treat diseases and can either increase the payment of your policy or not want to give you a policy at all. Also, they have had problems with the FDA (Food and Drug Administration) because they are giving information that can be misinterpreted as diagnostics of a disease and they are not approved by the FDA to do this. This is why they say: “We no longer offer our health-related genetic reports to new customers to comply with the U.S. Food and Drug Administration’s directive to discontinue new consumer access during our regulatory review process”. So, for now they are only offering the ancestry as well as other tools like how much of your DNA is from Neanderthals and finding relatives that have also used 23 & me to new clients.  

Moreover, it might not come as a shock but these people have competitors! There are other companies that provide similar services. One of these is the National Geographic, yes you read correctly, the National Geographic has what they call “The Genographic project” where they use the data acquired to map the evolution of mankind including the migration routes of ancestors. So not only do you obtain your ancestry information but also help in the research of the history of humans, which is pretty neat.


Another cool example, which I personally like, is the Wisdom panel company. They use this technology on pet dogs to determine their breed/s as well as the history behind that breed. This gives an opportunity to pet owners to know the history behind the breed of their specific dog.   
 As you can see a lot can come out of a few drops of spit. From genetic information that can open a world of antecedent knowledge of your family or even human race, to information that can determine your probability to obtain a disease, or even determine the race and history of your pet dog. It all comes from a single spit sample and single DNA sequence with its SNP variants. So from now on don’t underestimate the power of your spit, because with the appropriate technology and that spit, one can obtain a lot of valuable information.


Here is and extra video that shows how 23 & me processes the spit sample in the lab to obtain the results, FYI:  

https://www.youtube.com/watch?v=0gC8RQ7PemM 

References:

Wisdom panel, recovered 3/4/15 <http://www.wisdompanel.com/>
The Genographic project, recovered 3/4/15 <https://genographic.nationalgeographic.com/>
23 & me, recovered 3/4/15 <https://www.23andme.com/>



 


Sunday, March 1, 2015

Future of medicine: Our DNA can lead to personalized medicine. (Non-Scientific)

By Edgardo Lopez

Can you imagine that in the future all of us get a diagnosis of a certain disease and be prepare for a better treatment? In our DNA we store all the information about ourselves, like the color of your eyes, baldness or even the possibility of having the same disease as one of the members of your family (don’t be scare is just a example). Knowing the complexity of our DNA we can understand many aspects related to medical issues in human health and now with the new technologies that are in constant change we can approach a better understanding of our biological information. Personalized medicine is not more just for diagnostic, now we can prevent medical problems and attack them in a more personalize treatment.
The most common example of a possible target for a better treatment is cancer. Cancer can be obtain throw our life course thanks to possible mutations acquired over time, interaction with the environment and even variation in the information that our DNA stores. One important key of knowing what cause cancer are called oncogenes. The oncogenes are DNA information in form of genes that promotes cell growing, tumor development and control of our cells. Advances in studies related to breast cancer incorporate the molecular approach to their clinical areas, were genes are analyze in each patient, to understand how their cells behave.
To achieve a better-personalized medicine we need to develop new ways to analyze the complexity of the data obtain from the disease and the DNA level. A possible way to analyze how a disease behave is by knowing the patterns of genes or protein expression to see how cells or tissue end up in certain characteristics. Understanding the complexity of DNA information will help us to comprehend a medical problem in a different aspect that the traditional medicine cannot do. Other areas of study that can achieve a better understanding other than cancer could be in cardiovascular medicine, neuroscience, metabolism and much more. The main goal of personalize medicine is to develop novel diagnostics, therapeutic approach and personalize drug development. One of the issues related to personalize medicine is focus in the analytical methods and the efficiency of DNA technologies.  For a better diagnosis, the complexity is a fundamental key to predict how our DNA expresses different things comparing normal cells with cancer cells (example). A profiling (analysis) of DNA expression and protein expression can be a good way to compare. Developing profiles of each individual can predict future event knowing their DNA constitution and expression. Personalize medicine is the next generation of clinical approach for a better performance in health care by using multiple source of DNA data. This next step in health will develop more precise descriptions of diseases, therapy decisions, and even formulation of drugs.
Here is a great talk video of how Personalize Medicine is changing with the advance in new technologies and how this will benefit us as patients.  

Reference:
Mike West et. al. Embracing the complexity of genomic data for personalized medicine.

16:559–566 2006. ISSN 1088-9051/06 <http://www.genome.org/cgi/doi/10.1101/gr.3851306. >