stjude / learngenomics.dev Goto Github PK

Reviewing 01-data-sources.md, it occurs to me that Robert Allaway has assembled a similar list (used for hackathons) that you may want to copy or reference.

Firstly, many thanks for the website. I am unable to load the website learngenomics.dev.

Running in to ERR_NAME_NOT_RESOLVED . I've attached screen grab for reference.

learngenomics.dev on  main is 📦 v0.0.0 via ⬢ v16.13.0
➜ curl https://learngenomics.dev/
curl: (6) Could not resolve host: learngenomics.dev

learngenomics.dev on  main is 📦 v0.0.0 via ⬢ v16.13.0
➜ curl http://learngenomics.dev/
curl: (6) Could not resolve host: learngenomics.dev

https://learngenomics.dev/docs/biological-foundations/translation

"As shown in the amino acid lookup table below, other codons specify that translation should start or stop at a particular position." but in the table it says 'STOP' twice with no 'START'

Hi! I'm a representatively ignorant software engineer, so here's what I'm left wondering after reading the Biological Foundations and skimming the rest (may revisit another day).

Confusion Area 1:

DNA has two strands which complement each other according to A<->T and C<->G. If one strand says ATGCATGC, then the mirror strand must say TACGTACG.

Thoughts:

• These strands are "equivalent", right?
• So it doesn't really make sense to ask "Which one do we write down when sequencing?", right?

I think/thought the answers are "yes" and "correct".

But! In Transcription, one strand is used to create the single strand immature RNA which is turned into the single-strand mature RNA.

If the first strand was used, the mRNA would be AUGCAUGC. If the second strand was used, the mRNA would be UACGUACG. (Or maybe swap those around, because the mRNA is made by mirroring the thing... or whatever... point is, you'd get different things depending on which strand is used to create the mRNA.)

I figure, "sure, still equivalent, technically".

But! In Translation, AUG makes the met codon and UAC makes the tyr codon. Those sound very different! (Same for CCC vs GGG making pro vs gly, etc.)

So... in some way, it does matter "which strand" of the original DNA you're looking at or operating on.

What notion am I missing?

I have another confusion area around chromosomes, haplotype, and genotype that similarly raises a "Which base in which thing is salient?" type question, but I suspect it'll be ameliorated by resolution to the above.

The Alternative Splicing page
https://github.com/stjude/learngenomics.dev/blob/main/docs/06-advanced-topics/alternative-splicing.md
should explain whether the splicing process can take place only by skipping certain exons (e.g. we get exons 1, 2, 4 (exon 3 was skipped)), or whether it's also possible for exons to be rearranged (e.g. we get exons 1, 4, 2, 3). Or maybe even if a combination of both is possible (we get exons 1, 4, 2).

On Cells, Chromosomes, and Genomes, it says:

Each chromosome is composed of two DNA molecules (one from your father and one from your mother) and packaging proteins, or histones, that keep the DNA string neatly wound and help control which gene products are made in a given cell. For humans, there are normally 22 autosomes (chromosomes shared by both sexes) and a pair of sex chromosomes (XX for females or XY for males). Autosomes are numbered from 1 to 22 based on size, arranged from largest to smallest. The full set of chromosomes makes up the genome.

I am only a programmer who is self-learning biology, but this caught my eye as confusing compared to other things I have learned. Is it accurate to refer to chromosomes as singular units containing 2 DNA molecules, rather than pairs of chromosomes that each have one DNA molecule, inherited one from the father or the mother? Should this language be cleaned up a bit to consistently refer to pairs or not refer to pairs? My concern is that if one reads "22 autosomes... and a pair of sex chromosomes," that could be misinterpreted as a total of 24 chromosomes. I think what is really meant is "22 pairs of autosomes... and a pair of sex chromosomes" for 23 total pairs, or 46 total chromosomes.

Of course things get more complicated with the haploid egg/sperm cells, and I realize you are sacrificing some details for simplicity. However I am concerned that the current description is somewhat inconsistent and confusing.

Here are some resources (all free) - is there a section to include 'learn more'?

• Team Teri - my own journey to learn basic bioinformatics (from a CS perspective) - https://github.com/lynnlangit/TeamTeri
• GCP-for-Bioinformatics - https://github.com/lynnlangit/gcp-for-bioinformatics
• AWS-for-Bioinformatics - https://github.com/lynnlangit/aws-for-bioinformatics
• Learn WDL - https://github.com/openwdl/learn-wdl

One thing that confused at first when I got into bioinformatics/cancer biology were the words "germline" and "somatic" as those mean different things in general biology and cancer biology.

I wasn't sure how to fit the stuff below on the baselines-for-variation page, otherwise I would have submitted something like this in a pull request.

In the general context of biology, "germline" refers to a cell type, and means "cells that are involved in reproduction and can turn into the genetic information passed on to progeny" and "somatic" means "all the cells that are not involved in reproduction."

In cancer biology, "germline" refers to the genome and variants of the specific individual organism and means "the base genetic variants inherited from that organism's parents" and "somatic" means "Variants that occurred during the life of the organism in some cells but not others"

If you extract and sequence the DNA from almost any random sample of normal tissue, you can find that organism's germline variants. If you do the same from a tumor sample and screen out the background germline variants, you'll likely find the somatic variants that exist in that tumor.

In https://learngenomics.dev/docs/genomic-variation/structural-variation this line is a bit hard to understand: "After an SV event the original genomic sequence is interrupted by another out place of sequence, creating a breakpoint."

Consider rephrasing to: "After an SV event, if the original genomic sequence is interrupted by another out of place of sequence, this can create what is called a breakpoint." assuming that makes sense technically.

In this sentence: For humans, there are normally 22 autosomes (chromosomes shared by both sexes) and pair of sex chromosomes (XX for females or XY for males).
SHOULD be "and A pair of sex chromosomes".
--Ben
See https://learngenomics.dev/docs/biological-foundations/cells-genomes-dna-chromosomes

The content is great, but it would be nice if it could be read on an e-reader, which is highly preferable vs a mobile phone for long-form reading for some folks. Any plans to convert it? Epub would be great as it is standard and easily convertible to other formats. Thanks!