Brain Mapping

Of all of the techniques used in science, none seem so much like magic as brain mapping. From PET scans to MRIs the process manages to divine not only that thoughts are occurring and where, but how the different parts of the brain communicate with each other, and perhaps, how those parts make up us.

I asked my Human Anatomy and Physiology students to read through some papers in PLOS’s excellent Brain Mapping Methods: Functional MRI section.

Read through the comments to see what they found and which papers they liked!

Indolent vs Malignant Tumors

This concept continues to crop up and in a way it is tied to a concept that continually pops-up in science.

How can an observer tell the difference between dangerous and non-dangerous lab results when they both look the same early on?

As our ability to see into the human body improves with each technological step, we often find ourselves at the fork in the road. We can see that there is clearly a physical change, perhaps a small tumor, or a polyp, or perhaps a constellation of genes, or altered genes. That change could lead to a malignant tumor, a parasite, an amalgam of broken cells, that now wage a single-sided war with their host.

Then again; it might be nothing…

Dennis Normile tackles this in his March 4, 2016 article in Science “Epidemic of Fear”. In fact Sarah Fallon has a great perspective piece in Wired (Wired’s science journalism continues to get better and better).

Normile presents a very nice case for care when evaluating new screening data against past norms. In a case study that follows Fukushima related pediatric thyroid screenings, he presents both the initial driver of fear, in the form of screening results that suggested elevated rates of thyroid nodules in children. Further studies of a “normal” or “unexposed” population describe similar elevated rates of nodule detection in the thyroid, a result that suggests better detection, but not higher risk.

Fallon puts this in perspective, and provides the title of this post, indolent vs. malignant tumors. With each technological leap, we are better able to identify smaller and smaller clusters of cells within the human body. But these advances require further study to provide clues (read as markers) as to whether these clusters of cells will go on to become a malignant monster or perhaps lie dormant for the lifetime of the host. This is in no way an insignificant question. One path takes the patient into the world of invasive treatment, while the second suggests that no further treatment is warranted, while the cluster is small and treatable.

There are many ways forward that were not available to clinicians previously. One of the more promising are gene expression profiles that will be used to classify these early clusters of cells as taking an indolent path over a malignant one. This data has been collected for more than a decade now, and is already being used to assist with these decisions.

Hopefully it will continue so.

Meet the Epitranscriptome

In “Epigenetics: A new methyl mark on messengers” Anna M. Kietrys & Eric T. Kool describe a particular methylation step that used to be thought of as damage. This is the latest front in epigenetic changes.

We have studied methylation of histone proteins for some time, and recognizing that this type of modification is a form of regulation. This regulation can modify gene expression in a way that can be passed on to daughter cells and even inherited from one generation to the next.

As the change does not alter the sequence of the genome, but rather the expression properties of genes encoded by the genome, this class of modifications was described as epigenetic. For a deeper history see “A Brief History of Epigenetics” by Gary Felsenfeld from CSHL Press (perhaps not so brief).

The newly described N1-methyladenosine (m1A) methylation may well mark a mRNA for differential expression. The mechanics of this may occur at the level of splicing, wherein these marked pre-mRNAs are spliced more rapidly or efficiently. Speeding them to the cytoplasm quickly and increasing translational accessibility, thus increasing protein levels.

The m1a methylation patterns may also play a part in the regulation, in human and mouse, site preference could be found, while this was less pronounced in yeast. Finally, there is still the problem of which M1A methylations are damage, and which are true signals? The “epitranscriptome” (love the term) may just be coming into focus as a new form of epigenetic regulation.

Researching Gene-Drug Interactions – Part I

Let’s say you are interested in researching a gene. Or, maybe, let’s say you are interested in researching a drug.

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Or, maybe, just maybe, you want to know about a drug-gene interaction. Where do you find that data?

We have more and more data available to use every minute… which is a good thing. For a researcher, looking through this data the first time (or for the 10th time) the sheer amount of information available can be a little daunting. Initial searches for genes used to yield hundreds of results, and many of those results were incomplete records, or just plan confusing.

Things are improving. Head over to the National Center for Biotechnology Information and search for genes using the keyword “warfarin” and you will get a list of genes back that mention warfarin or have been associated with a record that mentions warfarin. Total hits as of 5 February 2016 was 58, with the top two being VKORC1 and CYP2C9, generally identified as two of the genes encoding products involved in warfarin efficacy.

There are other data sets that to date are even easier to use. Let’s try the same warfarin search on another resource: Online Mendelian Inheritance in Man (OMIM). The search here yields 35 hits, VKORC1 and CYP2C9 are again in the top four, but the first hit is COUMARIN RESISTANCE. A quick click and you are reading a well annotated description, almost a text book chapter, but with more than a hundred links to relevant information on the subject.

But where is all that drug interaction data coming from? PharmGKB provides a more in depth look at all of the gene variants that might influence the function of those genes and the drugs that they are associated with. The same warfain search brings us here, to a wealth of information. I will leave almost all of this data for later, but have a look at the material described in the Pathways segment. Here the role the warfarin plays in the associated gene products functional pathway is graphically displayed. The role that VKORC1 plays is readily apparent, and why warfarins suppression of its function can be seen to play a role in the clotting process.

These are just three sources, covering the same warfarin example. The barriers to this information continue to fall, providing more intuitive access. Perhaps by your second and third searches you will will be more focused on the information you want, rather than wondering how you got there.

When Will Genetic Testing Be Affordable?

In this weeks paper there is a curious statement that comes just towards the end:

The limited availability and cost of pharmacogenetic testing are additional challenges (Tucker, 2008). Most insurance plans will reimburse the cost of pharmacogenetic testing only if it is required by the FDA, medically necessary, or has proven clinical utility (Shin et al., 2009).

  • Margaret Mroziewicz, m.Sc. Rachel F. Tyndale, ph.D. “Pharmacogenetics: A Tool for Identifying Genetic Factors in Drug Dependence and Response to Treatment” Addiction Science & Clinical Practice—December 2010

There is much excitement surrounding genetic testing and of course in a Gene Technology class we discuss the implications of this sort of approach regularly. If we are looking at pharmacogenomics, or ancestral research the entire process hinges on the sequencing being affordable.

A hidden benefit of the genome project was the development of new technology for sequencing and this is exactly what happened. On a side note, the genome project was started with full knowledge that the current sequencing technology was insufficient for the project and it is this aspect that initially garnered comparisons to the Apollo project. With the completion of the genome project the cost of sequencing has continued to drop as the quality of that same sequencing has increased.

 

Sometime around 2014 the $1,000 genome race really started to heat up. Nature touched upon the topic here. And then in 2015 Veritas Genetics broke through with their PGP collaboration here.

And with that, the cost barriers seem to be falling, leaving the question of what’s next. Having your genome sequenced comes with allot of challenges, allot of information, both technically and at a deeper level, information with obvious health implications.

 

 

Report From The Frontlines: Science Isn’t Broken

Science Isn’t Broken It’s just a hell of a lot harder than we give it credit for.

Science Isn’t Broken
It’s just a hell of a lot harder than we give it credit for.

Great piece by by Christie Aschwanden with graphics by Ritchie King. Could have done without the expletives (makes it harder to share with younger kids), but other wise love the tone and the interactive examples. I wish that more science writing was done this way; fantastic to have a little widget embedded within the article that helps explain the statistics.

Short Guide To Presenting Scientific Material – Part 3 – Presentation

I had a public speaking teacher in college who used to sit in the back of the classroom and start to moan when the presentations got to boring. If the presentation didn’t improve she would crumple some paper and start to throw it at us, we all knew she was a total nut-job, but the cool thing was that she was always right. When she started to complain, it was only mirroring what the class was already thinking. When she was completely fed-up, we were completely bored. If the internet and the laptop had been invented yet, we would have all wandered away, instead we just stared blankly, hoping it would be over soon.

There are a bunch of things that you can do to engage your audience. Try all of these things, remember, SCIENCE IS TOUGH, GIVE THE AUDIENCE A BREAK!

  • Start off the right way. Introducing yourselves is always smart, even if everyone knows you. A presentation is just like welcoming someone into your house, greet those who are in the audience as you would a guest.
  • Try not to refer to other speakers with pronouns. Use names, it puts your audience at ease. Each time you introduce someone, say “[Name] will tell you more about [topic]. It let’s the audience know what is going to happen next, and who will tell them about it.
  • Talk to the audience. It is good to have reference cards or screen notes, but you must engage the audience. This can be very hard and it takes practice, as you often want to have reference cards to keep yourself on task. Practice reading a sentence or two and then looking up to make sure that your audience is with you.
  • Don’t read directly from the slides. It turns your back to the audience and worse often seems like you have never seen the material on the slides before.
  • Speakers should come out from behind the podium. The podium and all that stuff on it often acts a crutch, it lets the speaker hide behind a protective wall of wood, glass, metal, and technology. Don’t use it this way. Move around, use your body language to make points and engage the audience. Look at them, use their faces to gauge wether or not they understand (or care) about your topic.
  • If you are not presenting. Have a seat, you don’t have to stand there and feel funny. It looks odd to the audience.
    • If you cannot sit, them move off to the side and look interested in what the presenter is saying. Do not engage in side conversations or distract the audience in any way.
  • Watch out for “you knows”, “ahs”, “likes” and “ums”.
    • These are unavoidable when you first begin speaking in front of audiences, it will pass. Just be aware of it, and each time you speak it will become less frequent.
    • If you get nervous or confused about what you want to say next, take a break and have a sip of water. Ask if the audience has any questions while you think and get back on track.
  • If you want to take a quick audience survey, use a show of hands. An audience will often raise their hands before they speak.
    • Don’t throw questions out there and then wait for someone to answer as this gets awkward quickly. Have a backup plan, “let’s see a show of hands…”, often works.
  • Practice the entire presentation with all of the presenters there. Look for redundancy and remove it from the overall presentation.
  • If you are nervous when giving a presentation be sure to separate nervous laughter from actual laughter. The audience does not see the difference, so if you talk about robberies where people are killed, and you laugh, even if it is just nervous laughter, it will be misinterpreted.
  • Never guess at answers to questions you don’t know. Just admit you don’t know and you will look it up and get back to them. There is no way that you can know all the answers, the audience will understand.
    • If you feel it is something that you absolutely think you know, but are a little unsure, tell the audience that you are speculating, and you and they will have to check your answer.
  • Restate questions; it give you time to think and also let’s the questioner know that you understand what they are asking. This way the  the whole audience understands both the question and your response.