This lesson is only available in Korean for now.
Dr. Seok's Hunting for the Gene, First Steps

Out of twenty thousand genes,
you find the one in command

A KAIST team led by Prof. Kwang-Hyun Cho showed that lung cancer cells disguise themselves as fetal tissue to slip past the immune system, and found DDX54, the master regulator directing that disguise, through a three-stage ARACNe โ†’ VIPER โ†’ DIGGIT analysis.
Over these 20 lessons you rerun all three stages yourself on public TCGA raw data. Python runs right inside this page. There is nothing to install.

๐Ÿ Python๐Ÿ•ธ๏ธ regulatory networks๐Ÿ“ mutual information ๐Ÿงฎ VIPER activity inference๐ŸŽฏ DIGGIT๐Ÿ in vivo validation๐Ÿ‡ฌ๐Ÿ‡ง English
Start lesson 1 โ†’

How you'll learn

๐Ÿ’กUnderstanding by analogy

Mutual information is a game of twenty questions, a regulon is the staff list under one boss, VIPER is reading the boss from how the staff move. You get a picture of the meaning before you memorise the formula.

โ–ถ๏ธWith the real data

Not a stand-in dataset. You work with the expression, mutation and copy-number data of 515 TCGA lung adenocarcinoma patients and the raw GEO GSE285342 data, exactly as deposited.

๐Ÿ”ฌChecked against the paper

You put the regulator-score ranking you computed side by side with the actual values in the paper's supplementary Table S2A and argue out whether it matches.

๐Ÿ› ๏ธLearning by handling it

Every lesson has a laboratory widget โ€” turn the DPI tolerance, the regulon size and the regulator quantile cut-off yourself.

Full curriculum

01
๋ฉด์—ญ ์‚ฌ๋ง‰์˜ ์—ญ์„ค โ€” ํ‘œ์ ์ด ์ด๋ ‡๊ฒŒ ๋งŽ์€๋ฐ ์™œ ์•ˆ ์žกํž๊นŒ
ํ”„๋กœํ† ์ฝœ ยง1 ๋ชฉ์  ยท ์šฐ๋ฆฌ๊ฐ€ 20๊ฐ• ๋™์•ˆ ์ซ“์„ ์‚ฌ๊ฑด
โœ“
02
์žฌ๋ฃŒ์™€ ๋„๊ตฌ โ€” ARACNE ยท VIPER ยท DIGGIT 3๋‹จ ํŒŒ์ดํ”„๋ผ์ธ
ํ”„๋กœํ† ์ฝœ ยง2 ์žฌ๋ฃŒ ยท ์™œ ์„ธ ๋‹จ๊ณ„์—ฌ์•ผ ํ•˜๋Š”๊ฐ€
โœ“
03
ํ‘œ๋ณธ ๊ณ ๋ฅด๊ธฐ โ€” 11,070๋ช…์—์„œ ์‹œ์ž‘ํ•œ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I ์ค€๋น„ ยท ํ•ญ์›์ œ์‹œ ๊ฒฝ๋กœ๊ฐ€ ๋ฉ€์ฉกํ•œ ํ™˜์ž๋งŒ
โœ“
04
๋‘ ๋ฌด๋ฆฌ๋กœ ๊ฐ€๋ฅด๊ธฐ โ€” ์‚ฌ๋ง‰๊ณผ ์—ผ์ฆ์˜ ๊ฒฝ๊ณ„์„ 
ํ”„๋กœํ† ์ฝœ Phase I ์ค€๋น„ ยท ๋น„๊ตํ•  ๋‘ ๋ฌด๋ฆฌ๋ฅผ ์ •์˜ํ•œ๋‹ค
โœ“
05
๋ฉด์—ญ์‚ฌ๋ง‰ ์‹œ๊ทธ๋‹ˆ์ฒ˜ โ€” ๋„คํŠธ์›Œํฌ์— ๋˜์งˆ ์งˆ๋ฌธ์ง€ ๋งŒ๋“ค๊ธฐ
ํ”„๋กœํ† ์ฝœ Phase I ยท ARACNE ์•ž์˜ ์ค€๋น„ ๋‹จ๊ณ„
โœ“
06
์ƒํ˜ธ์ •๋ณด๋Ÿ‰ โ€” ์ƒ๊ด€๊ณ„์ˆ˜๊ฐ€ ๋ชป ๋ณด๋Š” ๊ด€๊ณ„๋ฅผ ๋ณธ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-1 ยท ARACNE ์˜ ์‹ฌ์žฅ
โœ“
07
ARACNE โ‘  โ€” ์ „์‚ฌ์ธ์ž์™€ ํ‘œ์ ์„ ์ž‡๋Š”๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-1 ยท ์ƒํ˜ธ์ •๋ณด๋Ÿ‰ ๋ฌธํ„ฑ๊ณผ ๋ถ€ํŠธ์ŠคํŠธ๋žฉ 100ํšŒ
โœ“
08
ARACNE โ‘ก โ€” ๊ฐ„์ ‘ ๋งํฌ๋ฅผ ์ž˜๋ผ ๋‚ด๊ณ  ๋ ˆ๊ทค๋ก ์„ ๋งŒ๋“ ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-1 ยท ๋ฐ์ดํ„ฐ ์ฒ˜๋ฆฌ ๋ถ€๋“ฑ์‹(DPI)
โœ“
09
VIPER โ‘  โ€” ๋ถ€ํ•˜๋“ค์˜ ์›€์ง์ž„์œผ๋กœ ์ƒ์‚ฌ๋ฅผ ์ฝ๋Š”๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-2 ยท ๊ฐ€์ƒ ํ”„๋กœํ…Œ์˜ค๋ฏน์Šค๋ผ๋Š” ๋ฐœ์ƒ
โœ“
10
VIPER โ‘ก โ€” ์ผœ๋Š” ๋ถ€ํ•˜์™€ ๋„๋Š” ๋ถ€ํ•˜๋ฅผ ๊ตฌ๋ณ„ํ•œ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-2 ยท Mode of Regulation ๊ณผ ๊ฐ€์ค‘์น˜
โœ“
11
VIPER โ‘ข โ€” aREA ๋กœ ํ™œ์„ฑ์„ ์ˆซ์ž ํ•˜๋‚˜๋กœ ๋งŒ๋“ ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-2 ยท ์ˆœ์œ„ ๋†์ถ•๊ณผ NES
โœ“
12
ํ•ต์‹ฌ ์ „์‚ฌ์ธ์ž โ€” ํ™œ์„ฑ์€ ๋ณ€ํ•˜๋Š”๋ฐ ๋ฐœํ˜„์€ ์•ˆ ๋ณ€ํ•œ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-2 โ†’ I-3 ์„ ์ž‡๋Š” ๊ฒฐ์ •์  ๊ด€์ฐฐ
โœ“
13
DIGGIT โ‘  โ€” ์ „์‚ฌ์ธ์ž ์œ„์— ๋ˆ„๊ฐ€ ์žˆ๋Š”๊ฐ€
ํ”„๋กœํ† ์ฝœ Phase I-3 ยท ์œ ์ „์  ์›์ธ๊นŒ์ง€ ๊ฑฐ์Šฌ๋Ÿฌ ์˜ฌ๋ผ๊ฐ€๊ธฐ
โœ“
14
DIGGIT โ‘ก โ€” ๋ณต์ œ์ˆ˜๊ฐ€ ๋ฐœํ˜„์„ ๋Œ๊ณ  ๊ฐ€๋Š” ์œ ์ „์ž๋งŒ ๋‚จ๊ธด๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-3 ยท F-CNV ๋กœ ํ›„๋ณด ์ขํžˆ๊ธฐ
โœ“
15
DIGGIT โ‘ข โ€” ์กฐ๊ฑด๋ถ€ ์ƒํ˜ธ์ •๋ณด๋Ÿ‰์œผ๋กœ '๋ณ€์กฐ์ž'๋ฅผ ์žก๋Š”๋‹ค
ํ”„๋กœํ† ์ฝœ Phase I-3 ยท MINDy
โœ“
16
DIGGIT โ‘ฃ โ€” Regulator score, ๊ทธ๋ฆฌ๊ณ  ๋…ผ๋ฌธ๊ณผ์˜ ์ •๋ฉด ๋Œ€์กฐ
ํ”„๋กœํ† ์ฝœ Phase I-3 ๊ฒฐ๊ณผ ยท ์šฐ๋ฆฌ๋Š” ์–ด๋””๊นŒ์ง€ ์žฌํ˜„ํ–ˆ๋‚˜
โœ“
17
Phase II โ€” ์šฉ์˜์ž๋ฅผ ์‹ค์ œ๋กœ ๊บผ ๋ณธ๋‹ค
ํ”„๋กœํ† ์ฝœ Phase II ยท shRNA ยท CRISPR ยท ํ“จ๋กœ๋งˆ์ด์‹  ยท qRT-PCR ยท Western
โœ“
18
Phase III โ€” ํƒœ์•„ ๊ฐ€๋ฉด์ด ๋ฒ—๊ฒจ์ง€๋Š”๊ฐ€
ํ”„๋กœํ† ์ฝœ Phase III ยท ์˜์–‘๋ง‰ยทํƒœ๋ฐ˜ ์‹œ๊ทธ๋‹ˆ์ฒ˜ ยท CD38 ยท CD47
โœ“
19
Phase IV โ€” ๋™์ข…์ด์‹ ์ƒ์ฅ 4๊ตฐ๊ณผ ํ•ญ-PD1 ํˆฌ์—ฌ
ํ”„๋กœํ† ์ฝœ Phase IV ยท ์ ‘์ข… ยท ๋ฌด์ž‘์œ„ ๋ฐฐ์ • ยท ํˆฌ์•ฝ ์ผ์ •
โœ“
20
Phase V โ€” ์ข…์–‘ ยท ์ƒ์กด ยท ์นจ์œค, ๊ทธ๋ฆฌ๊ณ  ์žฌํ˜„ ํŒ์ •
ํ”„๋กœํ† ์ฝœ Phase V ยท ์šฐ๋ฆฌ๊ฐ€ ํ™•์ธํ•œ ๊ฒƒ๊ณผ ํ™•์ธํ•˜์ง€ ๋ชปํ•œ ๊ฒƒ
โœ“