--- a/2023.markdown Tue Nov 14 16:16:35 2023 -0500
+++ b/2023.markdown Wed Nov 15 13:41:22 2023 -0500
@@ -1884,3 +1884,605 @@
and my calendar/TODO list was extremely tedious. I think I've got it all mapped
out now though.
+# October 2023
+
+## 2023-10-01
+
+Put up a bunch of stuff for sale on the PIBS list. Need to declutter my
+apartment now that I've mostly moved in.
+
+Did a few hours of work on Lab 1 for BS521. Too much unproductive screwing
+around in R trying to figure out how to get decent fonts. Should be able to
+finish it up tomorrow though. Random notes jotted down from the process follow.
+
+Side-by-side figures in LaTeX:
+
+ \begin{figure}[h]
+ \begin{minipage}[t]{0.48\textwidth}
+ \includegraphics[width=\linewidth]{figures/bp-histogram}
+ \caption{Distribution of blood pressure among participants.}
+ \label{fig:bp-histogram}
+ \end{minipage}
+ \hfill
+ \begin{minipage}[t]{0.48\textwidth}
+ \includegraphics[width=\linewidth]{figures/bp-nqq}
+ \caption{Normal QQ plot of blood pressure values.}
+ \label{fig:bp-nqq}
+ \end{minipage}
+ \end{figure}
+
+
+Reasonable quantile plot in R:
+
+ qplot <- function(filename, data, label, main, ...) {
+ n = length(data)
+ plot(((1:n - 1)/(n - 1)), sort(data),
+ type = "l",
+ main = main,
+ xlab = "Quantile",
+ ylab = label,
+ ...)
+ }
+
+QQ plot with the damn line in R:
+
+ nqqplot <- function(data, ...) {
+ qqnorm(data, ...)
+ qqline(data)
+ }
+
+Reading in a CSV with specific column types:
+
+ data <- read_csv("EPID_521_lab_data.csv", col_types="iddfiffdffdd")
+
+Note that this seems to give you a "tibble", whatever the hell that is. Some
+kind of tidyverse thing? It's very confusing that everywhere you look there's
+a hairball of a mess of base R, tidyverse, and ggplot2 and everyone just assumes
+you understand which is part of what.
+
+Reordering levels:
+
+ data <- mutate(data, diet=factor(data$diet, levels=c("Poor", "Fair", "Good", "VeryGood", "Excellent")))
+
+
+Removing rows with `NA`s for e.g. the `cot` column:
+
+ data <- data[complete.cases(data$cot),]
+
+Histograms with specific bin widths, rather than a number of bins:
+
+ hist(data$age, breaks=seq(from=15, to=90, by=1), main="", xlab="Age")
+
+Multiple box plots in one image:
+
+ boxplot(bmi~sex, data=data)
+
+Marking and/or filtering on a boolean condition:
+
+ data$locot <- data$cot <= 0.011
+ locot <- subset(data, cot <= 0.011)
+ hicot <- subset(data, cot > 0.011)
+
+## 2023-10-02
+
+HG545 review this morning. Need to go back and review the first module again
+tomorrow since it's been a while.
+
+Finish BS521 lab 1, finally. That was a lot more work than I expected.
+
+Met with a professor about possible rotation. Need to chat with my advisor to
+see if there's special paperwork I'll need.
+
+## 2023-10-03
+
+BS521. Confidence intervals.
+
+BI500. Research writing.
+
+Finally got around to splitting my Vimrc into minimal and extra files, so I can
+sync the minimal one to servers and not hate myself when trying to edit. There's
+some jank involved around the colorschemes and `set termguicolors` but I think
+have have something that should work.
+
+PIBS800. Mentor/mentee relationships.
+
+## 2023-10-04
+
+Advising meeting. Need to do a couple of things in EdM and register for 602,
+but I'm currently blocked on both by other folks so I'm good for now.
+
+HG545 exam.
+
+## 2023-10-05
+
+Finished the HG545 exam last night. That was… deeply unpleasant.
+
+BS521. Hypothesis testing.
+
+BS521 reading.
+
+Read the paper for HG545. I get the general idea, and it seems like a pretty
+clear experiment. I wonder how much we'll stick to the paper vs going off topic
+this time.
+
+Needed to convert some PDF graphs to PNG to put in a presentation, but `convert`
+was whining about some security crap:
+
+ ><((°> convert n50.pdf n50.png
+ convert-im6.q16: attempt to perform an operation not allowed by the security policy `PDF' @ error/constitute.c/IsCoderAuthorized/421.
+
+Turns out there was a bug in ghostscript, which was fixed, but convert still
+doesn't trust it so won't convert stuff. Great. Have to edit
+`/etc/ImageMagick-6/policy.xml` and comment out these lines to make it behave:
+
+ <!-- disable ghostscript format types -->
+ <policy domain="coder" rights="none" pattern="PS" />
+ <policy domain="coder" rights="none" pattern="PS2" />
+ <policy domain="coder" rights="none" pattern="PS3" />
+ <policy domain="coder" rights="none" pattern="EPS" />
+ <policy domain="coder" rights="none" pattern="PDF" />
+ <policy domain="coder" rights="none" pattern="XPS" />
+
+Skimmed through the slides for HG545 tomorrow. It's nice to be able to get
+a preview of things again.
+
+## 2023-10-06
+
+HG545, class was about splicing. I feel much better about this module thanks to
+being able to prepare a bit with the preview last night.
+
+## 2023-10-07
+
+Installed <https://github.com/numcommand/num> — might come in handy here and
+there.
+
+## 2023-10-08
+
+Reread the paper for HG545. It's… a little clearer now? Though honestly it
+wasn't too bad before compared to the other papers. Just a lot of acronyms.
+Got a list of things to ask.
+
+## 2023-10-09
+
+HG545 this morning, about co/post-transcriptional modification. The downside of
+having slides is that people put a ton of things on them and you can't take
+notes fast enough. Need to go back over the slides and write down things once
+I get home so I don't forget them.
+
+## 2023-10-10
+
+BS521, hypothesis testing, p values, t distribution.
+
+BI500, code quality tips. Checked with Prof. Sartor and submitting a LaTeX PDF
+for the references homework is fine.
+
+Pinged a few students in a lab I'm interested in to see if they're willing to
+chat about their experience. Just need to nail down my third rotation and then
+I'll be all set.
+
+Ordered a used copy of the Grammar of Graphics book. I've read enough in the
+ebook copy from the library that I know I want the entire thing, even though
+it's quite expensive.
+
+Read chapter 4 of the book while the straggler genomes finish in the last batch,
+about variables and basic transformations on them. The book uses the ridiculous
+terms "homoscedasticity" and "heteroscedasticity" to mean "homogeneous variance"
+and "heterogeneous variance", which I *think* is the same idea as Cleveland's
+"monotone spread" (or possibly a more general version of it).
+
+I really wish the book wouldn't omit the axis-drawing code from the diagrams
+— it makes it unclear where each piece of the output is coming from. I think
+I *mostly* understand it, but would prefer if it were all explicit (even if it
+would make things a bit longer).
+
+Read chapter 5 too, on algebras. This was much, much more confusing and would
+have been much clearer with more explicit examples. Need to read this at least
+one more time to get it, I'm sure.
+
+Going back to take some notes for HG545 while they're still (vaguely) fresh in
+my mind. First: notes from the class on splicing.
+
+The "R-loop" terminology is confusing. It's inspired by the name "D-loop",
+which notes how DNA will unzip to show a loop when it's being duplicated (and
+there's a complementary strand bound to one side). "R-loop" *also* refers to
+the loop *in the DNA* when it's bound *to RNA* (e.g. when it's being
+transcribed). Again: the actual loop in an "R-loop" is a loop of DNA.
+
+An RNA molecule has 3 relevant sites when considering splicing:
+
+```
+ 5' exon | intron | 3' exon
+ ======AG|GUAAGU============================YNYURAY====Y₁₁NCAG|G==============
+ ↑
+ 5' Splice Site Branch Site 3' Splice Site
+```
+
+Note that in this case the branch site is specifically an adenine. That's
+important (reason comes later).
+
+One important aspect of RNA that allows it to be spliced (contrasted with DNA)
+is the hydroxyl group on the 2' carbon in RNA, which is not present in DNA
+(that's why it's *deoxy*ribose). That hydroxyl group is what attacks the
+phosphate bond at the 5' splice site and cleaves it apart (after being brought
+close to it by the spliceosome). That leaves a hydroxyl group exposed hanging
+off of the 5' exon, and in the next step *that* group is brought close to the 3'
+splice site and attacks it. Once that bond is broken the intron (as
+a lariat-shaped thing) floats away, and the exons are spliced together.
+
+The chemistry of the breaks is called "transesterification": two
+phosphodi*ester* bonds are broken (at intron/exon and exon/intron boundaries),
+and two more are created (one in the lariat, and the splice between exons).
+
+(Of course like everything in biology, in reality it's all a giant mess and there
+are multiple kinds of splicing, including self-splicing.)
+
+The spliceosome is a giant thing made of a bunch of different proteins and also
+5 RNAs that mediates splicing. The RNAs are important because those are what
+recognize the splice and branch sites through complementary pairing, e.g. at the
+5' splice site we have:
+
+ ____________
+ / U1 \ U1 component of spliceosome
+ \ /
+ \__CAUUCA__/
+ ┆┆┆┆┆┆
+ ==GUAAGU== RNA
+
+In a similar way, the U2 component binds to the branch site, but the binding
+sequence specifically skips the adenine at the site, which "extrudes" it from
+the RNA a little bit:
+
+ extruded adenine
+ ↓
+ A
+ ======U A C U A C======= RNA
+ ┆ ┆ ┆ ┆ ┆ ┆
+ .——C A U U C A——.
+ / \
+ / U2 \ U2 component of spliceosome
+ \___________________/
+
+Alternate splicing is also a big deal, because it allows the creation of many
+different mRNAs from the same gene by bringing together different exon/intron
+boundaries to be spliced instead of always splicing the closest one.
+
+Of course there's other complications too, like splicing enhancers and silencers
+that can recruit/block the splicing machinery.
+
+Skimmed over tomorrow's HG545 slides so I don't have to go in blind again. Seems
+pretty reasonable, though the end seems pretty rushed and I *think* it's
+relevant to one of the questions in the homework. Need to pay attention at the
+end.
+
+PIBS800, how to read a research paper. I feel like I've had three versions of
+this presentation by different people at different times at this point.
+
+Started BS521 homework 5. A bit more confusing than the previous homeworks, and
+it's been a week or so since I touched LaTeX so I once again have to fight it
+every step of the way.
+
+## 2023-10-11
+
+HG545 this morning, about translation.
+
+VA onboarding after that. Took a couple of hours, but I now finally have
+a badge.
+
+Been reading the GoG book during some spare free minutes here and there.
+Skimming over a lot of the formalism, I still feel like this could be much
+improved by showing some full examples with everything laid out.
+
+Sketched out some answers to HG545 questions.
+
+Finished BS521 homework 5, turned it in.
+
+Cleaned up HG545 answers. Need to do one final pass tomorrow.
+
+## 2023-10-12
+
+BS521, started talking about two-distribution t tests.
+
+Finally got around to swapping my search engine on my phone to Kagi. The
+degoogling continues.
+
+I really need to figure out a decent way to do proper pivot tables in Postgres.
+From reading the docs it looks *surprisingly* janky for what I'd expect from
+Postgres.
+
+Read up on index operator classes, which was preventing Postgres from using an
+index when searching for a prefix of a string, e.g. `SELECT name FROM foo WHERE
+name LIKE 'pref%';`. Fixed by telling Postgres this index will be used with
+text patterns by e.g. `CREATE INDEX i__foo__name ON foo(name
+text_pattern_ops);`.
+
+## 2023-10-13
+
+HG545 discussion.
+
+## 2023-10-14
+
+Fall break.
+
+## 2023-10-15
+
+Did the BIOINF-500 homework on reference management/citation. Figured out how
+to get Latex set up to do references. Lots of jank, but I think I've got it
+working now. JabRef produces a `.bib` file as its database. Then in the Latex
+document, add a preamble:
+
+
+ \usepackage[
+ backend=biber,
+ style=nature,
+ sorting=ynt
+ ]{biblatex}
+ \addbibresource{sjl.bib}
+
+Cite things with `\cite{foo}` and `\cite{bar,baz}`. Then `\printbibliography`
+to put the references section into the paper there.
+
+This is complicated by the fact that you have to run `biber` between runs of
+`pdflatex`, so I kludged together a `mklatex` script that does something
+horrifying like `pdflatex; biber; pdflatex; pdflatex` to actually make the damn
+document. Gross.
+
+I really need to get my latex stuff into a set of files, rather than
+copy/pasting everything into every single document.
+
+## 2023-10-18
+
+Back from fall break. Time to get back into the swing of classes.
+
+HG545 this morning, starting the section about transposable elements. The
+professor put up slides, videos, and a narrative document in advance which is
+really great — I was able to prepare and not be completely lost.
+
+Read over animal ethics stuff for tomorrow. Need to consider if I want to
+really do a rotation with animal subjects. I'm a little less sure now.
+
+## 2023-10-19
+
+BS521 this morning. The second half of the class has a different lecturer,
+starting today. Talked about paired t-tests (which are essentially just doing
+a one-sample t-test on the difference of the paired values) and ANOVA for
+many-sample t-testing.
+
+First PIBS503 discussion section. This is (I think) the only one that's in
+person, and it's in the middle of goddamn nowhere on the North Campus.
+I managed to find my way there, but dear god are these buildings confusing.
+
+BISTRO at 4. Topic: HMMSTR, using HMMs for tandem repeat copy number detection
+from ONT reads.
+
+Need to remember to ask Alan if he has any suggestions on reading material
+I should look at over the weekend before I start with him on Monday.
+
+## 2023-10-20
+
+HG545. More on transposable elements, this time about LTR retrotransposons.
+
+Met with Bob about rotation paperwork.
+
+Last day of my first rotation! I think it went well. Looking forward to trying
+out more things in the next few rotations, but this one was great!
+
+## 2023-10-21
+
+Finished reading the HG545 paper, finally. It was long, but a lot more clear
+than the other papers thanks to the supplementary material actually *explaining*
+things. So even though it was a little tedious to get through with so many
+abbreviations, I think I preferred it overall to the other papers so far.
+
+Finally got around to hooking up a keyboard shortcut for `switch-yubikeys`
+since I find myself actually using it a lot again, now that I'm not working from
+home full time.
+
+Sent my lab notebook to the PI, which is my last official act of the rotation.
+
+Swapped out a fresh VM for my next rotation. Keeping the old one around for
+a few weeks in case I end up needing anything from it. Glad I've got everything
+scripted up around this — much easier to do it this time.
+
+Started BS Lab 2. Not going to do the extra credit this time, I just don't have
+the spare time at the moment. Too much going on all at once.
+
+Installed Weechat+wee-slack and irssi on my laptop. Going to give irssi a try
+for a while as an IRC client, which would let me reserve Weechat (which I don't
+really like all that much) for Slack. Irssi config was a little janky, but
+I think I got something dogfoodable for now.
+
+Installed the Python lib for the next rotation on the VM in a venv.
+
+## 2023-10-22
+
+Finish BS lab 2. Didn't go the extra mile on this one either, still trying to
+catch up from break. I'm getting there though.
+
+Figured out some travel/break logistics for between semesters.
+
+Finished BS homework 7. I should be all caught up on stuff for that class
+(aside from reading, which goes quick) for a while now. Next big thing for it
+is the exam on 11/02.
+
+Got a couple of LaTeX snippets to remember after all the biostat stuff. First,
+often worth making shortcuts for frequently used stuff in a given assignment:
+
+ \def\h0{\textbf{H}_0}
+ \def\hA{\textbf{H}_A}
+ \def\tstar#1{t^\star_\textit{#1}}
+
+Adding spacing between equation lines with `\jot`:
+
+ \begin{equation*}
+ \setlength{\jot}{10pt}
+ \begin{split}
+ T & = \frac{\bar{X} - \mu_D}{s/\sqrt{n}} \\
+ & = \frac{-0.545 - 0}{8.887/\sqrt{200}} \\
+ & = \frac{-0.545}{0.6284058} \\
+ T & \approx -0.867 \\
+ \end{split}
+ \end{equation*}
+
+Started HG545 homework, just sketching out notes. Burned out before getting too
+far, will have to actually get a rough draft done tomorrow (then cleaned up on
+Tuesday).
+
+## 2023-10-23
+
+HG545, about the L1 transposition assaying and Alu.
+
+First day of the new lab rotation! Set up `black` on the laptop since I'll be
+doing Python. Ended up installing it into a venv and symlinking to the binary,
+which seems to have worked okay.
+
+Need to figure out how to get Irssi to autoload scripts properly and set up
+e.g. `/toggle awl_viewer` on startup so I don't have to do it by hand every
+time.
+
+Got a first draft of HW5 90% done. Will finish tomorrow.
+
+Did some reading for BS521. Still have a little left for Thursday.
+
+## 2023-10-24
+
+BS521 today. Got another intuitive explanation of ANOVA (which was nice) and
+talked about categorical CIs/hypothesis testing.
+
+BI500. Presentations by faculty who are looking to recruit students:
+
+1. Statistical/online bioinformatics.
+2. Cell lineage trees via imaging + ML. If only there was a way to kludge
+ something into mitosis that would tag descendant genomes ala service request
+ ID tagging (or even just e.g. a plasmid that would mutate quickly as
+ a clock).
+3. Head/neck cancer and ALS research via multiomics and large cohort studies.
+4. How molecular/biological clocks work.
+5. How cell cell signaling controls cell fate in human pluripotent stem cells.
+6. Exercise, multiomics, and wearables, cell communications and differential
+ expression with ML.
+7. Wearable and multiomics data to identify biomarkers for early
+ detection/prevention of disease.
+
+Should also look into the additional ones who couldn't be fit into timeslots to
+present.
+
+Lunch at Maizie's.
+
+PIBS 800 about grants, e.g.
+<https://rackham.umich.edu/funding/rackham-graduate-student-research-grant/>
+which can be done as a pre-candidate *and* candidate. I think I should get Cat
+to explain this to me in idiot terms so I can figure out all the stuff I'm
+missing.
+
+Met with study group for HG545 homework. I feel like I understand everything
+very well, but trying to fit a coherent explanation into the line limits of the
+homework is absolutely miserable.
+
+Finished HG545 homework. Walking unsteadily as I emerge from the prose-gutting
+facility covered in texual viscera and stinking of article blood, my filleting
+backspace key dull in its socket.
+
+## 2023-10-25
+
+HG545 discussion this morning. Chatted about a bunch of stuff, nothing too
+groundbreaking.
+
+Spent the rest of the day in the lab.
+
+Put together my new table at home. Looks nice.
+
+Reviewed the files for the next two 503 discussions this week. Nothing
+really surprising here.
+
+Did the BS521 reading for tomorrow.
+
+## 2023-10-26
+
+BS521 class this morning.
+
+I've got the 503 discussion thing at 2, need to figure out a good place to take
+that Zoom call. Maybe the study rooms at the top of THSL? Need to figure out
+how to reserve those at some point.
+
+PIBS 503 discussion class zoom meeting.
+
+Started reading the next HG545 paper and glanced over the slides. I wish we had
+lectures recorded like the last module.
+
+## 2023-10-27
+
+HG545 lecture. New module starts today, on replication.
+
+There's more than just one DNA Polymerase. Three main ones are called α, δ, and
+ε. Roughly, α starts, then hands off to δ. On the lagging strand, that's all
+it has time for before it falls off and the process starts again for the next
+Okazaki fragment. But on the leading strand, δ has time to hand off to ε, which
+is much more stable and can continue along the strand.
+
+Proofreading and mismatch repair are both very important. The initial
+polymerization process has an error rate somewhere around 10⁻⁶. Mismatch repair
+happens *in-line* with the replication process: DNA Pol doesn't like continuing
+from a mismatch based, so most of the time it will pause for a bit and the
+proofreading machinery that's also in the replication complex will chomp off the
+bad base, then DNA Pol will continue. Mismatch repair happens separately: one
+protein recognizes the mismatch and recruits another protein that excises the
+match *and a big chunk of the downstream strand*, and that whole chunk gets
+resynthesized.
+
+Another PIBS 503 class discussion zoom meeting. 3 down, 4 to go.
+
+## 2023-10-28
+
+Started digging into the HG545 paper. I hate that we only have 2 classes for
+this one, it feels far too rushed.
+
+## 2023-10-29
+
+Finished the second readthrough of the paper. I feel a little better now, but
+am still not perfectly sure on the questions.
+
+## 2023-10-30
+
+HG545 class, mostly on DNA repair. Makes the case that a lot of DNA repair
+reuses the same polymerases (e.g. δ) as replication (but not all, e.g.
+single-base repair uses something else (I think β?)), and you can kind of think
+of it as just another form of replication.
+
+Another important point: replication is not deterministic, because it doesn't
+have to be. As long as the whole genome (well, chromosome) gets replicated, it
+doesn't matter precisely where that replication started. This is very different
+from e.g. transcription, because starting in a different place would transcribe
+a different gene.
+
+Also important to define terms like lesion vs mutation: a lesion is detectable
+DNA damage, which then get fixed into place (in the "use fixer on the photo
+paper" sense, not the "repair" sense) by subsequent replication.
+
+I think I'm feeling a little better about the homework questions now after
+talking through it a bit. Need to get some rough drafts sketched out for when
+I meet with the study group tomorrow.
+
+## 2023-10-31
+
+BS521. Chi-square test.
+
+BI500. Senior student discussion panel. Each gave us advice:
+
+* Find a mentor that works for you (specifically what *you* need, will be
+ different for everyone).
+* Use these years as training, not 100% research.
+* Take care of yourself, set boundaries. Marathon, not sprint.
+* Take ownership of your time here, do things that'll help you grow.
+* The novelty of a PhD will wear off, stick with it.
+* Have hobbies.
+* Keep a calendar.
+* Talk with your peers a lot, don't keep everything to yourself.
+
+PIBS800. Career planning.
+
+Met with HG545 folks. This module was a bit better than the rest.
+
+Finished and submitted HG545 homework.
+
+Made BS521 note sheet for the exam Thursday.
+
--- a/README.markdown Tue Nov 14 16:16:35 2023 -0500
+++ b/README.markdown Wed Nov 15 13:41:22 2023 -0500
@@ -5,608 +5,6 @@
[TOC]
-# October 2023
-
-## 2023-10-01
-
-Put up a bunch of stuff for sale on the PIBS list. Need to declutter my
-apartment now that I've mostly moved in.
-
-Did a few hours of work on Lab 1 for BS521. Too much unproductive screwing
-around in R trying to figure out how to get decent fonts. Should be able to
-finish it up tomorrow though. Random notes jotted down from the process follow.
-
-Side-by-side figures in LaTeX:
-
- \begin{figure}[h]
- \begin{minipage}[t]{0.48\textwidth}
- \includegraphics[width=\linewidth]{figures/bp-histogram}
- \caption{Distribution of blood pressure among participants.}
- \label{fig:bp-histogram}
- \end{minipage}
- \hfill
- \begin{minipage}[t]{0.48\textwidth}
- \includegraphics[width=\linewidth]{figures/bp-nqq}
- \caption{Normal QQ plot of blood pressure values.}
- \label{fig:bp-nqq}
- \end{minipage}
- \end{figure}
-
-
-Reasonable quantile plot in R:
-
- qplot <- function(filename, data, label, main, ...) {
- n = length(data)
- plot(((1:n - 1)/(n - 1)), sort(data),
- type = "l",
- main = main,
- xlab = "Quantile",
- ylab = label,
- ...)
- }
-
-QQ plot with the damn line in R:
-
- nqqplot <- function(data, ...) {
- qqnorm(data, ...)
- qqline(data)
- }
-
-Reading in a CSV with specific column types:
-
- data <- read_csv("EPID_521_lab_data.csv", col_types="iddfiffdffdd")
-
-Note that this seems to give you a "tibble", whatever the hell that is. Some
-kind of tidyverse thing? It's very confusing that everywhere you look there's
-a hairball of a mess of base R, tidyverse, and ggplot2 and everyone just assumes
-you understand which is part of what.
-
-Reordering levels:
-
- data <- mutate(data, diet=factor(data$diet, levels=c("Poor", "Fair", "Good", "VeryGood", "Excellent")))
-
-
-Removing rows with `NA`s for e.g. the `cot` column:
-
- data <- data[complete.cases(data$cot),]
-
-Histograms with specific bin widths, rather than a number of bins:
-
- hist(data$age, breaks=seq(from=15, to=90, by=1), main="", xlab="Age")
-
-Multiple box plots in one image:
-
- boxplot(bmi~sex, data=data)
-
-Marking and/or filtering on a boolean condition:
-
- data$locot <- data$cot <= 0.011
- locot <- subset(data, cot <= 0.011)
- hicot <- subset(data, cot > 0.011)
-
-## 2023-10-02
-
-HG545 review this morning. Need to go back and review the first module again
-tomorrow since it's been a while.
-
-Finish BS521 lab 1, finally. That was a lot more work than I expected.
-
-Met with a professor about possible rotation. Need to chat with my advisor to
-see if there's special paperwork I'll need.
-
-## 2023-10-03
-
-BS521. Confidence intervals.
-
-BI500. Research writing.
-
-Finally got around to splitting my Vimrc into minimal and extra files, so I can
-sync the minimal one to servers and not hate myself when trying to edit. There's
-some jank involved around the colorschemes and `set termguicolors` but I think
-have have something that should work.
-
-PIBS800. Mentor/mentee relationships.
-
-## 2023-10-04
-
-Advising meeting. Need to do a couple of things in EdM and register for 602,
-but I'm currently blocked on both by other folks so I'm good for now.
-
-HG545 exam.
-
-## 2023-10-05
-
-Finished the HG545 exam last night. That was… deeply unpleasant.
-
-BS521. Hypothesis testing.
-
-BS521 reading.
-
-Read the paper for HG545. I get the general idea, and it seems like a pretty
-clear experiment. I wonder how much we'll stick to the paper vs going off topic
-this time.
-
-Needed to convert some PDF graphs to PNG to put in a presentation, but `convert`
-was whining about some security crap:
-
- ><((°> convert n50.pdf n50.png
- convert-im6.q16: attempt to perform an operation not allowed by the security policy `PDF' @ error/constitute.c/IsCoderAuthorized/421.
-
-Turns out there was a bug in ghostscript, which was fixed, but convert still
-doesn't trust it so won't convert stuff. Great. Have to edit
-`/etc/ImageMagick-6/policy.xml` and comment out these lines to make it behave:
-
- <!-- disable ghostscript format types -->
- <policy domain="coder" rights="none" pattern="PS" />
- <policy domain="coder" rights="none" pattern="PS2" />
- <policy domain="coder" rights="none" pattern="PS3" />
- <policy domain="coder" rights="none" pattern="EPS" />
- <policy domain="coder" rights="none" pattern="PDF" />
- <policy domain="coder" rights="none" pattern="XPS" />
-
-Skimmed through the slides for HG545 tomorrow. It's nice to be able to get
-a preview of things again.
-
-## 2023-10-06
-
-HG545, class was about splicing. I feel much better about this module thanks to
-being able to prepare a bit with the preview last night.
-
-## 2023-10-07
-
-Installed <https://github.com/numcommand/num> — might come in handy here and
-there.
-
-## 2023-10-08
-
-Reread the paper for HG545. It's… a little clearer now? Though honestly it
-wasn't too bad before compared to the other papers. Just a lot of acronyms.
-Got a list of things to ask.
-
-## 2023-10-09
-
-HG545 this morning, about co/post-transcriptional modification. The downside of
-having slides is that people put a ton of things on them and you can't take
-notes fast enough. Need to go back over the slides and write down things once
-I get home so I don't forget them.
-
-## 2023-10-10
-
-BS521, hypothesis testing, p values, t distribution.
-
-BI500, code quality tips. Checked with Prof. Sartor and submitting a LaTeX PDF
-for the references homework is fine.
-
-Pinged a few students in a lab I'm interested in to see if they're willing to
-chat about their experience. Just need to nail down my third rotation and then
-I'll be all set.
-
-Ordered a used copy of the Grammar of Graphics book. I've read enough in the
-ebook copy from the library that I know I want the entire thing, even though
-it's quite expensive.
-
-Read chapter 4 of the book while the straggler genomes finish in the last batch,
-about variables and basic transformations on them. The book uses the ridiculous
-terms "homoscedasticity" and "heteroscedasticity" to mean "homogeneous variance"
-and "heterogeneous variance", which I *think* is the same idea as Cleveland's
-"monotone spread" (or possibly a more general version of it).
-
-I really wish the book wouldn't omit the axis-drawing code from the diagrams
-— it makes it unclear where each piece of the output is coming from. I think
-I *mostly* understand it, but would prefer if it were all explicit (even if it
-would make things a bit longer).
-
-Read chapter 5 too, on algebras. This was much, much more confusing and would
-have been much clearer with more explicit examples. Need to read this at least
-one more time to get it, I'm sure.
-
-Going back to take some notes for HG545 while they're still (vaguely) fresh in
-my mind. First: notes from the class on splicing.
-
-The "R-loop" terminology is confusing. It's inspired by the name "D-loop",
-which notes how DNA will unzip to show a loop when it's being duplicated (and
-there's a complementary strand bound to one side). "R-loop" *also* refers to
-the loop *in the DNA* when it's bound *to RNA* (e.g. when it's being
-transcribed). Again: the actual loop in an "R-loop" is a loop of DNA.
-
-An RNA molecule has 3 relevant sites when considering splicing:
-
-```
- 5' exon | intron | 3' exon
- ======AG|GUAAGU============================YNYURAY====Y₁₁NCAG|G==============
- ↑
- 5' Splice Site Branch Site 3' Splice Site
-```
-
-Note that in this case the branch site is specifically an adenine. That's
-important (reason comes later).
-
-One important aspect of RNA that allows it to be spliced (contrasted with DNA)
-is the hydroxyl group on the 2' carbon in RNA, which is not present in DNA
-(that's why it's *deoxy*ribose). That hydroxyl group is what attacks the
-phosphate bond at the 5' splice site and cleaves it apart (after being brought
-close to it by the spliceosome). That leaves a hydroxyl group exposed hanging
-off of the 5' exon, and in the next step *that* group is brought close to the 3'
-splice site and attacks it. Once that bond is broken the intron (as
-a lariat-shaped thing) floats away, and the exons are spliced together.
-
-The chemistry of the breaks is called "transesterification": two
-phosphodi*ester* bonds are broken (at intron/exon and exon/intron boundaries),
-and two more are created (one in the lariat, and the splice between exons).
-
-(Of course like everything in biology, in reality it's all a giant mess and there
-are multiple kinds of splicing, including self-splicing.)
-
-The spliceosome is a giant thing made of a bunch of different proteins and also
-5 RNAs that mediates splicing. The RNAs are important because those are what
-recognize the splice and branch sites through complementary pairing, e.g. at the
-5' splice site we have:
-
- ____________
- / U1 \ U1 component of spliceosome
- \ /
- \__CAUUCA__/
- ┆┆┆┆┆┆
- ==GUAAGU== RNA
-
-In a similar way, the U2 component binds to the branch site, but the binding
-sequence specifically skips the adenine at the site, which "extrudes" it from
-the RNA a little bit:
-
- extruded adenine
- ↓
- A
- ======U A C U A C======= RNA
- ┆ ┆ ┆ ┆ ┆ ┆
- .——C A U U C A——.
- / \
- / U2 \ U2 component of spliceosome
- \___________________/
-
-Alternate splicing is also a big deal, because it allows the creation of many
-different mRNAs from the same gene by bringing together different exon/intron
-boundaries to be spliced instead of always splicing the closest one.
-
-Of course there's other complications too, like splicing enhancers and silencers
-that can recruit/block the splicing machinery.
-
-Skimmed over tomorrow's HG545 slides so I don't have to go in blind again. Seems
-pretty reasonable, though the end seems pretty rushed and I *think* it's
-relevant to one of the questions in the homework. Need to pay attention at the
-end.
-
-PIBS800, how to read a research paper. I feel like I've had three versions of
-this presentation by different people at different times at this point.
-
-Started BS521 homework 5. A bit more confusing than the previous homeworks, and
-it's been a week or so since I touched LaTeX so I once again have to fight it
-every step of the way.
-
-## 2023-10-11
-
-HG545 this morning, about translation.
-
-VA onboarding after that. Took a couple of hours, but I now finally have
-a badge.
-
-Been reading the GoG book during some spare free minutes here and there.
-Skimming over a lot of the formalism, I still feel like this could be much
-improved by showing some full examples with everything laid out.
-
-Sketched out some answers to HG545 questions.
-
-Finished BS521 homework 5, turned it in.
-
-Cleaned up HG545 answers. Need to do one final pass tomorrow.
-
-## 2023-10-12
-
-BS521, started talking about two-distribution t tests.
-
-Finally got around to swapping my search engine on my phone to Kagi. The
-degoogling continues.
-
-I really need to figure out a decent way to do proper pivot tables in Postgres.
-From reading the docs it looks *surprisingly* janky for what I'd expect from
-Postgres.
-
-Read up on index operator classes, which was preventing Postgres from using an
-index when searching for a prefix of a string, e.g. `SELECT name FROM foo WHERE
-name LIKE 'pref%';`. Fixed by telling Postgres this index will be used with
-text patterns by e.g. `CREATE INDEX i__foo__name ON foo(name
-text_pattern_ops);`.
-
-## 2023-10-13
-
-HG545 discussion.
-
-## 2023-10-14
-
-Fall break.
-
-## 2023-10-15
-
-Did the BIOINF-500 homework on reference management/citation. Figured out how
-to get Latex set up to do references. Lots of jank, but I think I've got it
-working now. JabRef produces a `.bib` file as its database. Then in the Latex
-document, add a preamble:
-
-
- \usepackage[
- backend=biber,
- style=nature,
- sorting=ynt
- ]{biblatex}
- \addbibresource{sjl.bib}
-
-Cite things with `\cite{foo}` and `\cite{bar,baz}`. Then `\printbibliography`
-to put the references section into the paper there.
-
-This is complicated by the fact that you have to run `biber` between runs of
-`pdflatex`, so I kludged together a `mklatex` script that does something
-horrifying like `pdflatex; biber; pdflatex; pdflatex` to actually make the damn
-document. Gross.
-
-I really need to get my latex stuff into a set of files, rather than
-copy/pasting everything into every single document.
-
-## 2023-10-18
-
-Back from fall break. Time to get back into the swing of classes.
-
-HG545 this morning, starting the section about transposable elements. The
-professor put up slides, videos, and a narrative document in advance which is
-really great — I was able to prepare and not be completely lost.
-
-Read over animal ethics stuff for tomorrow. Need to consider if I want to
-really do a rotation with animal subjects. I'm a little less sure now.
-
-## 2023-10-19
-
-BS521 this morning. The second half of the class has a different lecturer,
-starting today. Talked about paired t-tests (which are essentially just doing
-a one-sample t-test on the difference of the paired values) and ANOVA for
-many-sample t-testing.
-
-First PIBS503 discussion section. This is (I think) the only one that's in
-person, and it's in the middle of goddamn nowhere on the North Campus.
-I managed to find my way there, but dear god are these buildings confusing.
-
-BISTRO at 4. Topic: HMMSTR, using HMMs for tandem repeat copy number detection
-from ONT reads.
-
-Need to remember to ask Alan if he has any suggestions on reading material
-I should look at over the weekend before I start with him on Monday.
-
-## 2023-10-20
-
-HG545. More on transposable elements, this time about LTR retrotransposons.
-
-Met with Bob about rotation paperwork.
-
-Last day of my first rotation! I think it went well. Looking forward to trying
-out more things in the next few rotations, but this one was great!
-
-## 2023-10-21
-
-Finished reading the HG545 paper, finally. It was long, but a lot more clear
-than the other papers thanks to the supplementary material actually *explaining*
-things. So even though it was a little tedious to get through with so many
-abbreviations, I think I preferred it overall to the other papers so far.
-
-Finally got around to hooking up a keyboard shortcut for `switch-yubikeys`
-since I find myself actually using it a lot again, now that I'm not working from
-home full time.
-
-Sent my lab notebook to the PI, which is my last official act of the rotation.
-
-Swapped out a fresh VM for my next rotation. Keeping the old one around for
-a few weeks in case I end up needing anything from it. Glad I've got everything
-scripted up around this — much easier to do it this time.
-
-Started BS Lab 2. Not going to do the extra credit this time, I just don't have
-the spare time at the moment. Too much going on all at once.
-
-Installed Weechat+wee-slack and irssi on my laptop. Going to give irssi a try
-for a while as an IRC client, which would let me reserve Weechat (which I don't
-really like all that much) for Slack. Irssi config was a little janky, but
-I think I got something dogfoodable for now.
-
-Installed the Python lib for the next rotation on the VM in a venv.
-
-## 2023-10-22
-
-Finish BS lab 2. Didn't go the extra mile on this one either, still trying to
-catch up from break. I'm getting there though.
-
-Figured out some travel/break logistics for between semesters.
-
-Finished BS homework 7. I should be all caught up on stuff for that class
-(aside from reading, which goes quick) for a while now. Next big thing for it
-is the exam on 11/02.
-
-Got a couple of LaTeX snippets to remember after all the biostat stuff. First,
-often worth making shortcuts for frequently used stuff in a given assignment:
-
- \def\h0{\textbf{H}_0}
- \def\hA{\textbf{H}_A}
- \def\tstar#1{t^\star_\textit{#1}}
-
-Adding spacing between equation lines with `\jot`:
-
- \begin{equation*}
- \setlength{\jot}{10pt}
- \begin{split}
- T & = \frac{\bar{X} - \mu_D}{s/\sqrt{n}} \\
- & = \frac{-0.545 - 0}{8.887/\sqrt{200}} \\
- & = \frac{-0.545}{0.6284058} \\
- T & \approx -0.867 \\
- \end{split}
- \end{equation*}
-
-Started HG545 homework, just sketching out notes. Burned out before getting too
-far, will have to actually get a rough draft done tomorrow (then cleaned up on
-Tuesday).
-
-## 2023-10-23
-
-HG545, about the L1 transposition assaying and Alu.
-
-First day of the new lab rotation! Set up `black` on the laptop since I'll be
-doing Python. Ended up installing it into a venv and symlinking to the binary,
-which seems to have worked okay.
-
-Need to figure out how to get Irssi to autoload scripts properly and set up
-e.g. `/toggle awl_viewer` on startup so I don't have to do it by hand every
-time.
-
-Got a first draft of HW5 90% done. Will finish tomorrow.
-
-Did some reading for BS521. Still have a little left for Thursday.
-
-## 2023-10-24
-
-BS521 today. Got another intuitive explanation of ANOVA (which was nice) and
-talked about categorical CIs/hypothesis testing.
-
-BI500. Presentations by faculty who are looking to recruit students:
-
-1. Statistical/online bioinformatics.
-2. Cell lineage trees via imaging + ML. If only there was a way to kludge
- something into mitosis that would tag descendant genomes ala service request
- ID tagging (or even just e.g. a plasmid that would mutate quickly as
- a clock).
-3. Head/neck cancer and ALS research via multiomics and large cohort studies.
-4. How molecular/biological clocks work.
-5. How cell cell signaling controls cell fate in human pluripotent stem cells.
-6. Exercise, multiomics, and wearables, cell communications and differential
- expression with ML.
-7. Wearable and multiomics data to identify biomarkers for early
- detection/prevention of disease.
-
-Should also look into the additional ones who couldn't be fit into timeslots to
-present.
-
-Lunch at Maizie's.
-
-PIBS 800 about grants, e.g.
-<https://rackham.umich.edu/funding/rackham-graduate-student-research-grant/>
-which can be done as a pre-candidate *and* candidate. I think I should get Cat
-to explain this to me in idiot terms so I can figure out all the stuff I'm
-missing.
-
-Met with study group for HG545 homework. I feel like I understand everything
-very well, but trying to fit a coherent explanation into the line limits of the
-homework is absolutely miserable.
-
-Finished HG545 homework. Walking unsteadily as I emerge from the prose-gutting
-facility covered in texual viscera and stinking of article blood, my filleting
-backspace key dull in its socket.
-
-## 2023-10-25
-
-HG545 discussion this morning. Chatted about a bunch of stuff, nothing too
-groundbreaking.
-
-Spent the rest of the day in the lab.
-
-Put together my new table at home. Looks nice.
-
-Reviewed the files for the next two 503 discussions this week. Nothing
-really surprising here.
-
-Did the BS521 reading for tomorrow.
-
-## 2023-10-26
-
-BS521 class this morning.
-
-I've got the 503 discussion thing at 2, need to figure out a good place to take
-that Zoom call. Maybe the study rooms at the top of THSL? Need to figure out
-how to reserve those at some point.
-
-PIBS 503 discussion class zoom meeting.
-
-Started reading the next HG545 paper and glanced over the slides. I wish we had
-lectures recorded like the last module.
-
-## 2023-10-27
-
-HG545 lecture. New module starts today, on replication.
-
-There's more than just one DNA Polymerase. Three main ones are called α, δ, and
-ε. Roughly, α starts, then hands off to δ. On the lagging strand, that's all
-it has time for before it falls off and the process starts again for the next
-Okazaki fragment. But on the leading strand, δ has time to hand off to ε, which
-is much more stable and can continue along the strand.
-
-Proofreading and mismatch repair are both very important. The initial
-polymerization process has an error rate somewhere around 10⁻⁶. Mismatch repair
-happens *in-line* with the replication process: DNA Pol doesn't like continuing
-from a mismatch based, so most of the time it will pause for a bit and the
-proofreading machinery that's also in the replication complex will chomp off the
-bad base, then DNA Pol will continue. Mismatch repair happens separately: one
-protein recognizes the mismatch and recruits another protein that excises the
-match *and a big chunk of the downstream strand*, and that whole chunk gets
-resynthesized.
-
-Another PIBS 503 class discussion zoom meeting. 3 down, 4 to go.
-
-## 2023-10-28
-
-Started digging into the HG545 paper. I hate that we only have 2 classes for
-this one, it feels far too rushed.
-
-## 2023-10-29
-
-Finished the second readthrough of the paper. I feel a little better now, but
-am still not perfectly sure on the questions.
-
-## 2023-10-30
-
-HG545 class, mostly on DNA repair. Makes the case that a lot of DNA repair
-reuses the same polymerases (e.g. δ) as replication (but not all, e.g.
-single-base repair uses something else (I think β?)), and you can kind of think
-of it as just another form of replication.
-
-Another important point: replication is not deterministic, because it doesn't
-have to be. As long as the whole genome (well, chromosome) gets replicated, it
-doesn't matter precisely where that replication started. This is very different
-from e.g. transcription, because starting in a different place would transcribe
-a different gene.
-
-Also important to define terms like lesion vs mutation: a lesion is detectable
-DNA damage, which then get fixed into place (in the "use fixer on the photo
-paper" sense, not the "repair" sense) by subsequent replication.
-
-I think I'm feeling a little better about the homework questions now after
-talking through it a bit. Need to get some rough drafts sketched out for when
-I meet with the study group tomorrow.
-
-## 2023-10-31
-
-BS521. Chi-square test.
-
-BI500. Senior student discussion panel. Each gave us advice:
-
-* Find a mentor that works for you (specifically what *you* need, will be
- different for everyone).
-* Use these years as training, not 100% research.
-* Take care of yourself, set boundaries. Marathon, not sprint.
-* Take ownership of your time here, do things that'll help you grow.
-* The novelty of a PhD will wear off, stick with it.
-* Have hobbies.
-* Keep a calendar.
-* Talk with your peers a lot, don't keep everything to yourself.
-
-PIBS800. Career planning.
-
-Met with HG545 folks. This module was a bit better than the rest.
-
-Finished and submitted HG545 homework.
-
-Made BS521 note sheet for the exam Thursday.
-
# November 2023
## 2023-11-01
@@ -928,3 +326,25 @@
their grad students later this week.
PIBS800.
+
+Finished the 3D printing course on the library site so I can potentially use the
+3D printers there now. Still need to learn how to make stuff in e.g. TinkerCAD
+first I think.
+
+Read the review papers for HG545 tomorrow to prime my brain. I'm still
+expecting it to be a lot to take in.
+
+Started the TinkerCAD tutorials. Seems simple enough so far.
+
+## 2023-11-15
+
+HG545, start of the Epigenetics module.
+
+Registered for classes. Mostly went smoothly except for two:
+
+* Needed to swap out the BS521 lab for a lab session on Mondays. Given that
+ I haven't been really using the lab sessions much at all, this is fine.
+* Need instructor permission for BIOINF-545, and also apparently it's Tuesday
+ and *Friday*? Strange set of days. So much for my free Fridays. Oh well, at
+ least Thursdays will be less wild I guess.
+