BIOL398-04/S15:Class Journal Week 10

William A. C. Gendron

1. Overall, do you think this paper was clearly written? Why or why not?
   • I agree with Alyssa. The paper had a lot of information and seemed a bit scattered. Despite the difficulty to read it, it seems necessary to address such a complex system. It may also be easier for someone who has an extensive background in yeast biology and therefore be more managable.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • The results seem quite thorough and the papers that they cited seemed complete as well so probably. I have not done a microarray before or several other assays that they mention, but I think with the proper training it should be possible. As for the statistics, I am unfamiliar with some of the tests as well, but I imagine I could look up most of those tests online and then apply them if I have the proper programs for them.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to see a more focused analysis on some of these genes. They are good at listing the changes, but on an individual scale they do not understand the mechanisms necessarily. I also think that it would be interesting to look into other ways to control the cells more directly. I also wonder if anyone has tried creating an even bigger picture of all of this. Why not test these cells over a whole range of temperatures, nutrients, and flow rate and then variance for each temperature, nutrient and flow rate? The idea would be to create a large number of permutations that attempt to cover almost every possible state the cells could be in. Admittedly, that project would be annoying to work on, but it would be interesting to see if we can create a big picture of yeast cells.

William A. C. Gendron 00:26, 24 March 2015 (EDT)

Kara M Dismuke

Group 2: Jeff, Natalie, Kara
Vu, T. T., & Vohradsky, J. (2007). Nonlinear differential equation model for quantification of transcriptional regulation applied to microarray data of Saccharomyces cerevisiae. Nucleic acids research, 35(1), 279-287. doi: 10.1093/nar/gkl1001

1. Overall, do you think this paper was clearly written? Why or why not?
   • For the most part, I would contend that the article was clearly written. Many aspects of the article (equations, concepts, figures, etc.) presented were very detailed and so ingrained in both mathematics and biology that it required a close reading (done multiple times) in order for one to gain an understanding of the material. There were definitely parts that, I believe, could have been presented clearly. For instance, in assigning activator and repressor variable names, it would have made more sense to label activator as "a" and repressor as "b" rather than the other way around (as it was done). In addition, it would have been helpful had they used different colors or a line with bigger dashes in order for the reader to more easily distinguish between the lines of Figure 1. The article definitely presupposes a working knowledge of both high-level biology and high-level mathematics, but upon careful readings and analyses, it was not inaccessible, as I was able to understand the majority of the article's content.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • Because this wasn't a typical "laboratory" experiment, it was difficult to identify a real "methods" section of the paper; however, I do think I understand the procedure that Vu and Vohradsky used. With this being said, I don't feel confident in my ability to do the iterations of the calculations and create some sort of automation within MATLAB for doing so (which it would seem to require since this methodology is so computationally heavy). As far as the data analysis goes, I am not sure if I would be able to interpret the data in the same way so as to identify the "best fitting regulator" as a match to a particular target gene.
3. What else would you like to know about their methods, results, and future directions?
   • I think it would be helpful to have access to the papers referred to in the article. In addition to trying myself to replicate this study in an attempt to validate by obtaining the same results, I think I would also like to extend this study to span a greater number of target genes considered and include a greater number of regulators in the pool of possible regulators.

--Kara M Dismuke 01:35, 23 March 2015 (EDT)

Lucia I. Ramirez

Paper: Lee, T. I., Rinaldi, N. J., Robert, F., Odom, D. T., Bar-Joseph, Z., Gerber, G. K., Hannett, N. M., Harbison, C. T., Thompson, C. M., Simon, I., Zeitlinger, J., Jennings, E. G., Murray, H.L ., Gordon, D. B., Ren, B., Wyrick, J. J., Tagne, J. B., Volkert, T. L., Fraenkel, E., Gifford, D. K. & Young, R. A. (2002). Transcriptional regulatory networks in Saccharomyces cerevisiae. Science, 298(5594), 799-804. DOI: 10.1126/science.1075090

1. Overall, do you think this paper was clearly written? Why or why not?
   • I think this paper had clear writing, but it contained over-complicated wording. Overall, the paper explained clearly how the biological aspect of transcriptional regulators could be understood as motifs and then compiled into an algorithm.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • Given time constraints, I would not be able to reproduce their experiments and data analysis because they analyzed 106 time 3 regulators. The analyses of this large data set would take too long to reproduce. On the other hand, analyzing regulators through their created algorithm would be a faster approach to reproduce their data analysis, since a lot of the biological analysis has been very well researched.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to see their algorithm. I would also like to see other verification made besides the cell cycle.

Lucia I. Ramirez 00:48, 24 March 2015 (EDT)

Tessa A. Morris

1. I think that the article was pretty clearly written, however there were a few parts that used fairly confusing language. The description of the figures, were overall helpful and easy to understand, but there were a few figures that I had trouble understanding.
2. I do not think that I could reproduce this experiment from the methodology section. I am familiar with some of the wet work done in the lab, (PCR and Western Blot Analysis)which are techniques that I did in biochemistry lab. However, the actual mathematical model was not thoroughly enough described for us to be able to reproduce the data analysis. They did cite sources that might be helpful in understanding what exactly to do, but from the paper I do not think that I could reproduce the experiment.
3. A lot of the methods and results were pretty vague. I think that they could expand these sections in order for us to be able to do future research. They explained that future research and knowledge of these networks can be helpful in understanding the human body and fighting disease, but I think they should expand a little more on this and explain more specifically how these could help.

Tessa A. Morris 01:55, 23 March 2015 (EDT)

Natalie Williams

1. Overall, do you think this paper was clearly written? Why or why not?
   • This article was clearly written in that there were many details in it. Because of those descriptions, I had to read the article multiple times to come close to even grasping an understanding of it. However, if someone did not have somewhat basic information about the concepts mentioned in this experiment, they would have been lost. Some of their language was circular, so it took a while to make some of those connections. Furthermore, their descriptions could have been misinterpreted easily depending in how you perceived their words depending on how they described some of their figures and methods.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • I believe that if provided with the code used to run MATLAB, that I could reproduce their experiment. I do not believe that I would be able to analyze the data as well as they did seeing in how at least 100 iterations for each individual regulator pair (40 targets with 184 potential regulators) were run. Not knowing exactly how they derived their equations as well would cause trouble for me in reaching similar conclusions.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to work through their equations and learn more about how they compiled their project and concept together. I would also like to see what their results would be like now due to YEASTRACT's updated database. With their algorithm, they could test and look at the regulation of genes under varying environmental conditions and stressors.

Natalie Williams 02:43, 23 March 2015 (EDT)

Kristen M. Horstmann

1. Overall, do you think this paper was clearly written? Why or why not?
   • I think the article was relatively pretty clear as the majority of it was possible to understand. However, as Tessa already stated, there were a few word choices that were questionable and got me more hung up on what they were trying to say more than what they were actually saying.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • Definitely not. Some of their techniques were briefly glossed over (for example, they did not discuss what conditions they grew their yeast in other than the 3 mediums they were grown in, and my group and I had a lengthy discussion/debate over how many times they repeated their experiment) and this information is too vital for recreating it for there to be a debate over it. This type of data should be straightforward and clearly stated in order to allow the readers to recreate it. Also, there was absolutely no discussion on the algorithm or computational model used to create the network they kept discussing. There was very little information on which data was even inputted into the model. While discussing the algorithm, the article simply stated "Additional details... are available upon request." This might be fine for those who seriously want to replicate the model, but not for students like me who are simply trying to understand.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to know more specific details on the computational model. I would like to know what work went into it, what data goes into it, and what the output looks like-- does it output the pictorial model given in the paper, or does it output a bunch of numbers that they must then analyze? I would also like to hear more of their thoughts on what type of genomes they are planning on extending this model into. They kept saying how with the motifs as building blocks and no background knowledge is necessary to create the model, the model can be used as a template for analyzing larger genomes other than the yeast genome. I was curious on what larger genomes they had in mind, if they're looking at strains of viruses or bacteria, or a large organism?

Kristen M. Horstmann 03:02, 23 March 2015 (EDT)

Alyssa Gomes

1. Overall, do you think this paper was clearly written? Why or why not?
   • I think the article was somewhat clearly written. There was some points in it where I wasn't quite sure what the authors were trying to show exactly, but rather just put all of their information in the paper. There was almost a surplus of information but without deeper discussion linking it back to the main point of the article, determining transcriptional changes in yeast when exposed to cold shock.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • I think if I had the help of a well-informed scientist, I could. As a math major, I am not quite sure what some methods meant in terms of their processes for analyzing data. The authors linked a lot of their own processes to other papers rather than explaining the process themselves, so if I reviewed all of the other sources that the article linked back to, maybe I could, but it would take a lot of steps to find the other individual papers and determine their own purposes.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to know the individual importance of each research article that our own article linked to. As I read through it, linguistically, it made sense, but in a bigger sense, the authors made so many references to six other papers that without knowing those other papers, it was a bit confusing what their methods were. They also used a lot of outside sources for analyzing the genome but didn't describe much of what they used to analyze their own data gathered from this experiment. I was unsure what data came from their tests and what data came from external sources.

Alyssa N Gomes 19:05, 23 March 2015 (EDT)

Lauren M. Magee

1. Overall, do you think this paper was clearly written? Why or why not?
   • The paper does seem to be clearly written, even though some aspects of their study remain unclear to me. I think further outlining their methods and their reasoning for experimental choices, would be greatly beneficial. However, I did understand what their figures and the comparisons they were making between the transcriptome and batch cultures so I feel as though that contributed to the bulk of my learning from this paper.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • The methods in this paper offer up a lot of information. However, they reference different papers in their methods section, that they pulled experimental processes from, but they don't themselves outline to the reader their process. For me as a reader, these citations stand to block my understanding, because I have to stop reading the paper to go look up the citation they offer if I want to gain a more holistic view of their experiment. It can be hard to find these articles, get access to these articles, or find the method highlighted in the paper. I could potentially reproduce their experiment, but it requires me to do a more in-depth analysis of their cited articles, because I couldn't reproduce it based on just the information they offer in their own "materials & method" section.
3. What else would you like to know about their methods, results, and future directions?
   • I wish they explained their reasoning for certain choices they made in this experiment. There a lot of details given in the methods of this paper that seem extraneous to me. Why did they choose to keep certain factors constant, why did they choose to measure the changes in other factors? We did they feel the need to incorporate so many different articles and use those methods instead of their own? Would it have been more beneficial to focus on only one article? What hypotheses were they trying to test and how did their methods reflect that?

Lauren M. Magee 12:14, 24 March 2015 (EDT)

Karina Alvarez

1. Overall, do you think this paper was clearly written? Why or why not?
   • I thought that this paper was a bit vague and unclear in some parts. For example, in the materials and methods it was not very specific in exact techniques.
2. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?
   • As mentioned above, I do not think that I could clearly execute the same experiment or corroborate their work even if I did get the same results because I could not be sure if we used the same methods. Much of it referenced other works which I could review, but it was difficult to follow it chronologically.
3. What else would you like to know about their methods, results, and future directions?
   • I would like to read more about the implications of this beyond microbiology, as in its applications in the world. I would also like to know more about what the next steps are, as in what an experiment could potentially be to follow this up.

• Karina Alvarez 02:56, 24 March 2015 (EDT):

Jeffrey Crosson

1. Overall, do you think this paper was clearly written? Why or why not?

• It was written pretty well, but the main complaint is that the graphs and charts are not labelled well.

1. Based on what is written in the methods section, do you think you could reproduce their experiments and data analysis?

• Not completely. I'm a mechanical engineer.

1. What else would you like to know about their methods, results, and future directions?

• I want to know exactly how they derived all of their equations.

Jeffrey Crosson 2:59, 24 March 2015 (EDT)