Podcast Appearance: Toggle Town by Ryan Tomich

I recently met an incredible student from Butte High School, Ryan Tomich, who is interested in making small towns even better through the use of technology. I was fortunate to be a guest on his podcast dedicated to this subject. The questions led me to essentially give a brief summary of my career and also highlighted my recent switch to embracing computational biology in my research and teaching.

Upcoming episodes of this podcast will feature Janet Coe, who will discuss the new Nursing Simulation Lab at Montana Tech. Later, John McKee, will describe his experience with starting a distillery in Butte in Butte, which is aptly called Headframe Spirits.

Taking Up Computational Biology

Computational Biology? Few of the resources that I describe here specifically address computational biology. My approach has been to first know biology and then learn computer programming while always having the question, “How can I apply this to my research?” in the back of my mind.

False Starts: After multiple attempts to learn a programming language throughout my life, the COVID-19 pandemic lockdown had the upside of letting me (finally) make progress using toward bringing computational biology into my research and teaching activities. So, roughly two years into my coding journey, I am emerging from the world of tutorials to the world of applying my knowledge to real-world projects and scientific problems.

What have the past two years looked like? Hours upon hours of both (on sale) Udemy courses and free tutorials. Learning any new topic can be a roller coaster nicely summarized by the Dunning-Kruger Effect.

Paid Courses: Udemy is my go-to source when I’m learning a new topic. Using the Dunning-Kruger Effect as a framework for thinking about my learning approach, I feel like the Udemy courses layout a roadmap for how to study the topic at hand. This way, I can look through the Udemy curriculum and skip past both the Peak of “Mount Stupid” and the Valley of Despair. That is, by seeing the road ahead, I accept that I am at the low end of the Slope of Enlightenment. Most of the courses I have purchased consist of at least 20 hours of curriculum and, because of this, they contain roughly a 3-credit college course for $12-15 when on sale. My course purchases went from a “vanilla” Python-specific curriculum to branching out into scientific Python, data science, machine learning, application development, computer vision, Git, and data engineering.

Free Stuff: I am impressed with the amount of free curriculum that programmers make available to the public. YouTube, GitHub, Kaggle, freeCodeCamp, and some material at Codecademy are the tip of the iceberg for freely-available resources for learning computer programming. From these sites, the two languages I have studied most are Python and JavaScript.

What’s next? I consider this journey as a lifelong learning experiment. My decades as a biologist and my newfound passion for computer programming will undoubtedly be a fruitful combination. While my first two years of this combination have gone largely undocumented, I am reminded of the saying, “The difference between science and screwing around is that, in science, you write it down.”

Here’s to becoming more scientific about my personal computational biology learning experiment. -Joel

Next Generation Sequencing 1: Overview Questions

For Biotechnology

Questions to answer while watching this video:

  1. What are the four types of sequencing that will be discussed in this video.
  2. What was the cost of the original human genome sequencing effort?  What was the cost (using Sanger sequencing) immediately after the completion in 2001?
  3. What does it mean that DNA is made of anti-parallel strands?
  4. DNA can be denatured by raising the temperature.  What “R” word did Dr. Chow use as a synonym for annealing the matching strands?
  5. How does a polymerase know what new nucleotide to add to the 3′ hydroxyl group of a growing DNA strand?
  6. What does dNTP stand for?  What are the four types of dNTPs?
  7. What are two ways that a fluorescent terminator differs from the dNTPs?
  8. In a Sanger sequencing-based PCR reaction, how many primers are added?
  9. In a Sanger sequencing-based PCR reaction, which molecules are more common: dNTPs or fluorescent terminators?
  10. What is a typical length of sequence that can be acquired using traditional (Sanger) sequencing?
  11. The Human Genome project used genomes from fewer than 10 people.  How many genomes need to be sequenced to better understand the functions of genes?
  12. Advances in sequencing technology from what company was behind the drops in sequencing costs around the years 2007, 2010, and 2015?
  13. The results from sequencing one stretch of DNA is called a “read”.  How many reads can be obtained from a run on a 384-well plate Sanger sequencing instrument vs. a NovaSeq instrument?
  14. How many gigabases of sequences can be obtained on the Sanger vs. NovaSeq instruments?
  15. What is the cost of sequencing a human genome with the latest Illumina technology (at the time this video was made)?
  16. When showing the different sizes of Illumina flow cells, what was the object that was used as a reference to show scale?
  17. Which spelling do you prefer: adapter or adaptor?
  18. The adaptor sequences have two parts: primer binding sites and capture sequences. 
    1. Once the (denatured) DNA has been loaded into the flow cell, which adaptor sequence part is hybridized to other single-stranded DNA first?
    2. How many copies of the original ssDNA are found in a cluster by the time the sequencing primer is added?
  19. In fluorescent reversible terminator chemistry, which carbon of the ribose sugar is the terminator molecule attached to?
  20. Once the terminator molecule is removed, what functional group resides at that carbon of the ribose sugar?
  21. What is the sequence of the first cluster that Dr. Chow walks through?
  22. What is the limit of the read length for this sequencing approach?
  23. What is the solution for the problem created when two cluster are so close together that they partially overlap?
  24. What is an advantage of switching from 4-color to 2-color chemistry?
  25. What is the pore size in the Oxford Nanopore system’s membranes?
  26. Detectors measure a change in what electrical property as a ssDNA flows through the pore?
  27. How many ssDNA molecules can flow through the pore at the same time?
  28. What features are found on the 3′ carbon and 5′ carbon of the ribose sugar in nucleotides used in PacBio sequencing?
  29. How does a PacBio flow cell limit the number of ssDNA molecules being sequenced at a given position?
  30. Why is a movie created to “watch” the PacBio sequencing, rather than a single image per round like in Illumina sequence technologies?
  31. How does data from PacBio get “corrected” to make up for the 10-15% error rate during the reading of a single stretch of ssDNA?
  32. Why are sequencing technologies that produce long reads beneficial for genome assembly? (3 bullet points for this answer)
  33. Which medical application did you find to be the most interesting? Why?

Buster Bear Goes Fishing

For Animal Stories for Kids

Buster Bear was having a lazy day.  But as the sun reached higher into the sky, his fur started to get hot and his stomach was starting to growl. 

“All right” he said to himself.  “Time to get a move on.”

Slowly and methodically, Buster Bear started to head downhill to the Laughing Brook.  The movement felt good to his well-rested muscles and the water ahead looked inviting. 

As he approached the Laughing Brook, Buster noticed that he wasn’t the only one that had thought about having fish as a mid-morning snack.  Once he was close, he realized that it was Little Joe Otter.  He also came to realize that the otter had been successful.  Little Joe Otter had a nice big trout in his mouth!

Buster Bear crept up to the unsuspecting otter and snarled.  As you can imagine, poor Little Joe Otter panicked at the sound, dropped the fish, and dove into the nearby water. 

“Just as I had hoped!” Buster Bear thought as he pounced on the trout before it flip-flopped its way down the stream bank.

Little Joe Otter popped his head out of the water of the water and stared coldly at Buster Bear’s mouth. 

Buster Bear stubbornly stood there and eventually said, “If you would like the fish back, just come get it.”

This did nothing to get Little Joe Otter to stop his unblinking gaze, so Buster Bear repeated his half-hearted offer.  “Come get your fish if you want it.”

Furious, Little Joe Otter dove under the water and slipped downstream until he met Billy Mink.  It didn’t take long to tell Billy about his encounter with Buster Bear.  Billy Mink listened to Little Joe’s tale and nodded sympathetically.  However, being a practical sort of animal, Billy Mink could only say, “There’s not much you can do about it, is there?”

Stewing in his anger, Little Joe Otter thought over his options until a plot for revenge took root in his mind.  Without a word, Little Joe Otter took to the water again and made his way upstream until he spotted Buster Bear.

It was clear that one fish did not satisfy the lazy bear’s appetite, so Buster Bear was progressing from one deep pool to the next.  Little Joe Otter picked up on Buster’s plan and moved quickly into action.  He first went to the pool Buster Bear was going to next.  Once there, he swam at a frantic pace in circles to scare away the fish in the pool and disturb the mud to make the water murky.

Buster Bear fished unsuccessfully there for a while and, discouraged, moved on to the next pool only to find the conditions to be similar.  All day long, Little Joe Otter sabotaged the lazy bear’s fishing.  Buster Bear’s stomach continued to growl and Little Joe Otter’s stomach joined in the chorus. 

Biology connection: Food resources, like fish, are prized by many different types of animals.  The battle for food is called competition.  The population size of one type of animal is often limited not only by the amount of food in an area but also by whether other types of animals eat that food, too.

Re-write of “Thornton Burgess Bedtime Stories” chapter 1.