Hi there, I struggled with this for a bit at the beginning of the competition and am just now getting my head around what we are trying to do (classify) w.r.t. this competition. I figured I would make this discussion post to share my understanding and allow others to comment/clarify as necessary.
\nSTARTING WITH THE COMPETITION DESCRIPTION
\n\n\nThe presence of a specific genetic sequence in the tumour known as MGMT promoter methylation has been shown to be a favourable prognostic factor and a strong predictor of responsiveness to chemotherapy.
\n
MY INTERPRETATION
\nThis is a good start. We know we are going to be predicting (binary classification) the presence of a genetic sequence (MGMT promoter methylation?) from mpMRI scans of patients with gliomas. We can also understand that this classification will help identify if a patient (more specifically their glioma) will respond favourably to chemotherapy.
\nNEXT WE LOOK AT A PAPER ATTEMPTING A SIMILAR TASK AND TARGET THEIR DESCRIPTION
\n\n\nMGMT is a DNA repair enzyme that protects normal and glioma cells from alkylating chemotherapeutic agents. The methylation of the MGMT promoter is an example of epigenetic silencing, which results in a loss of function of the MGMT enzyme and its protective effect on glioma cells. The survival benefit incurred by MGMT promoter methylation in patients treated with temozolomide (TMZ) was determined in 2005.1 Subsequent work by Stupp et al2 has shown that in patients who received both radiation and temozolomide, MGMT promoter methylation improved median survival compared with patients with unmethylated gliomas (21.7 versus 12.7 months).2 Long-term follow-up from that initial study has further substantiated the survival benefit.2,3As a result, determining MGMT promoter methylation status is an important step in predicting survival and determining treatment.
\n
MY TL;DR UNDERSTANDING
\nCORRECTION TO THE ABOVE INFORMATION WAS COMPLETED ON AUGUST 27, 2021 TO REFLECT THE COMMENT FROM USER @ivgona (thank you!!!)
\nSO IN SHORT:
\nSo it's essentially binary classification indicating whether or not someone's glioma will have a better chance of responding to chemo just from MRI scans. Very cool!
\nI hope this helps! Please don't hesitate to correct or improve my understanding.
", "messages": [ { "id": 1488861, "postDate": "2021-08-24T14:41:37.370Z", "content": "Hi there, I struggled with this for a bit at the beginning of the competition and am just now getting my head around what we are trying to do (classify) w.r.t. this competition. I figured I would make this discussion post to share my understanding and allow others to comment/clarify as necessary.
\nSTARTING WITH THE COMPETITION DESCRIPTION
\n\n\nThe presence of a specific genetic sequence in the tumour known as MGMT promoter methylation has been shown to be a favourable prognostic factor and a strong predictor of responsiveness to chemotherapy.
\n
MY INTERPRETATION
\nThis is a good start. We know we are going to be predicting (binary classification) the presence of a genetic sequence (MGMT promoter methylation?) from mpMRI scans of patients with gliomas. We can also understand that this classification will help identify if a patient (more specifically their glioma) will respond favourably to chemotherapy.
\nNEXT WE LOOK AT A PAPER ATTEMPTING A SIMILAR TASK AND TARGET THEIR DESCRIPTION
\n\n\nMGMT is a DNA repair enzyme that protects normal and glioma cells from alkylating chemotherapeutic agents. The methylation of the MGMT promoter is an example of epigenetic silencing, which results in a loss of function of the MGMT enzyme and its protective effect on glioma cells. The survival benefit incurred by MGMT promoter methylation in patients treated with temozolomide (TMZ) was determined in 2005.1 Subsequent work by Stupp et al2 has shown that in patients who received both radiation and temozolomide, MGMT promoter methylation improved median survival compared with patients with unmethylated gliomas (21.7 versus 12.7 months).2 Long-term follow-up from that initial study has further substantiated the survival benefit.2,3As a result, determining MGMT promoter methylation status is an important step in predicting survival and determining treatment.
\n
MY TL;DR UNDERSTANDING
\nCORRECTION TO THE ABOVE INFORMATION WAS COMPLETED ON AUGUST 27, 2021 TO REFLECT THE COMMENT FROM USER @ivgona (thank you!!!)
\nSO IN SHORT:
\nSo it's essentially binary classification indicating whether or not someone's glioma will have a better chance of responding to chemo just from MRI scans. Very cool!
\nI hope this helps! Please don't hesitate to correct or improve my understanding.
", "rawMarkdown": "Hi there, I struggled with this for a bit at the beginning of the competition and am just now getting my head around what we are trying to do (classify) w.r.t. this competition. I figured I would make this discussion post to share my understanding and allow others to comment/clarify as necessary.\n\nI would like to comment on your understanding of what is MGMT and the promoter region:
\n\n\nThe MGMT gene promoter is a thing everyone has.
\nThis promoter protects tissues (BUT ALSO CANCER CELLS) from various things (INCLUDING CHEMOTHERAPY).
\n
MGMT (O6-Methylguanine-DNA Methyltransferase) is a protein (an enzyme to be precise) that repairs DNA, that's why it protects the cell from mutations.
\nOn the other hand, a promoter is a region before the gene that regulates the \"on/off\" of it. It's a signaling region for the RNA polymerase to attach and begin the transcription process.
\nTherefore, the methylation or \"silencing\" of the promoter means the RNA polymerase doesn't have the signaling to attach to the DNA and the MGMT enzyme won't be produced.
Thanks for the helpful information! I feel much better about my understanding of the relevant biology. I have updated my main post to reflect your comment and my subsequent learnings.
", "rawMarkdown": "Thanks for the helpful information! I feel much better about my understanding of the relevant biology. I have updated my main post to reflect your comment and my subsequent learnings.", "votes": 1 } ] }, { "id": 1489333, "postDate": "2021-08-24T22:19:52.457Z", "content": "Thanks for sharing. This explanation helped me to understand the competition task in a better way =)
", "rawMarkdown": "Thanks for sharing. This explanation helped me to understand the competition task in a better way =)", "votes": 2 }, { "id": 1488990, "postDate": "2021-08-24T16:17:40.800Z", "content": "Thanks for this, Darien! Very clear description of the entire process. I had not realised that MGMT methylation is actually good for the patient, since then they can benefit from chemo.
", "rawMarkdown": "Thanks for this, Darien! Very clear description of the entire process. I had not realised that MGMT methylation is actually good for the patient, since then they can benefit from chemo.", "votes": 2 }, { "id": 1494545, "postDate": "2021-08-28T18:52:49.077Z", "content": "methlation seem to work \"suppression\" mainly
", "rawMarkdown": "methlation seem to work \"suppression\" mainly" }, { "id": 1492483, "postDate": "2021-08-27T07:50:54.337Z", "content": "Yes. It helped to understand better. save my time.
", "rawMarkdown": "Yes. It helped to understand better. save my time." }, { "id": 1497239, "postDate": "2021-08-31T04:21:19.150Z", "rawMarkdown": "", "isDeleted": true }, { "id": 1488942, "postDate": "2021-08-24T15:48:54.507Z", "content": "Needed this, Thanks
", "rawMarkdown": "Needed this, Thanks", "votes": 1 } ], "comments": [ { "id": 1489594, "author_name": "IvGoNa", "author_url": "", "post_date": "2021-08-25T05:47:29.977000", "content": "I would like to comment on your understanding of what is MGMT and the promoter region:
\n\n\nThe MGMT gene promoter is a thing everyone has.
\nThis promoter protects tissues (BUT ALSO CANCER CELLS) from various things (INCLUDING CHEMOTHERAPY).
\n
MGMT (O6-Methylguanine-DNA Methyltransferase) is a protein (an enzyme to be precise) that repairs DNA, that's why it protects the cell from mutations.
\nOn the other hand, a promoter is a region before the gene that regulates the \"on/off\" of it. It's a signaling region for the RNA polymerase to attach and begin the transcription process.
\nTherefore, the methylation or \"silencing\" of the promoter means the RNA polymerase doesn't have the signaling to attach to the DNA and the MGMT enzyme won't be produced.
Thanks for the helpful information! I feel much better about my understanding of the relevant biology. I have updated my main post to reflect your comment and my subsequent learnings.
", "votes": 1, "replies": [] } ] }, { "id": 1489333, "author_name": "Cinthia Cristina Calchi Kleiner", "author_url": "", "post_date": "2021-08-24T22:19:52.457000", "content": "Thanks for sharing. This explanation helped me to understand the competition task in a better way =)
", "votes": 2, "replies": [] }, { "id": 1488990, "author_name": "Sofia Moschou", "author_url": "", "post_date": "2021-08-24T16:17:40.800000", "content": "Thanks for this, Darien! Very clear description of the entire process. I had not realised that MGMT methylation is actually good for the patient, since then they can benefit from chemo.
", "votes": 2, "replies": [] }, { "id": 1494545, "author_name": "mephiroth", "author_url": "", "post_date": "2021-08-28T18:52:49.077000", "content": "methlation seem to work \"suppression\" mainly
", "votes": 0, "replies": [] }, { "id": 1492483, "author_name": "Saurav Solanki", "author_url": "", "post_date": "2021-08-27T07:50:54.337000", "content": "Yes. It helped to understand better. save my time.
", "votes": 0, "replies": [] }, { "id": 1497239, "author_name": "", "author_url": "", "post_date": "2021-08-31T04:21:19.150000", "content": "", "votes": 0, "replies": [] }, { "id": 1488942, "author_name": "DeepUnderstanding", "author_url": "", "post_date": "2021-08-24T15:48:54.507000", "content": "Needed this, Thanks
", "votes": 1, "replies": [] } ], "raw_markdown_by_id": { "1488861": "Hi there, I struggled with this for a bit at the beginning of the competition and am just now getting my head around what we are trying to do (classify) w.r.t. this competition. I figured I would make this discussion post to share my understanding and allow others to comment/clarify as necessary.\n\n