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| Status |
Public on Aug 21, 2019 |
| Title |
The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Surgery to correct trichiasis is a key component of the WHO trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of individuals were orally administered with 100mg/day of doxycycline or placebo for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 24 from each treatment group. Within each treatment group, 12 individuals developed ECA. Treatment and outcome groups were matched by age, sex and baseline disease severity. qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.
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| Overall design |
One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of individuals were orally administered with 100mg/day of doxycycline or placebo for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 24 from each treatment group. Within each treatment group, 12 individuals developed ECA. Treatment and outcome groups were matched by age, sex and baseline disease severity.
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| Contributor(s) |
Derrick T, Habtamu E, Tadesse Z, Callahan EK, Worku A, Gashaw B, Macleod D, Mabey DC, Holland MJ, Burton MJ |
| Citation(s) |
37426632 |
|
Derrick T, Habtamu E, Tadesse Z, Callahan EK, Worku A, Gashaw B, Macleod D, Mabey DCW, Holland MJ, and Burton MJ. The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment. Wellcome Open Res 2019, 4:130. doi:10.12688/wellcomeopenres.15419.1
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| Submission date |
Aug 06, 2019 |
| Last update date |
Sep 11, 2023 |
| Contact name |
Tamsyn Ruth Derrick |
| E-mail(s) |
tamsyn.derrick@lshtm.ac.uk
|
| Phone |
02079272419
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| Organization name |
london school of hygiene and tropical medicine
|
| Street address |
keppel street
|
| City |
london |
| ZIP/Postal code |
WC1E 7HT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (96)
|
| GSM4010448 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0317] |
| GSM4010449 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0351] |
| GSM4010450 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0381] |
| GSM4010451 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0386] |
| GSM4010452 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0456] |
| GSM4010453 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0496] |
| GSM4010454 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0540] |
| GSM4010455 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0586] |
| GSM4010456 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0703] |
| GSM4010457 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0817] |
| GSM4010458 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0890] |
| GSM4010459 |
Placebo-arm, Good outcome, Baseline [A_0_T0_DT0960] |
| GSM4010460 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0317] |
| GSM4010461 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0351] |
| GSM4010462 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0381] |
| GSM4010463 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0386] |
| GSM4010464 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0456] |
| GSM4010465 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0496] |
| GSM4010466 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0540] |
| GSM4010467 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0586] |
| GSM4010468 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0703] |
| GSM4010469 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0817] |
| GSM4010470 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0890] |
| GSM4010471 |
Placebo-arm, Good outcome, 1 month post trichiasis surgery [A_0_T1_DT0960] |
| GSM4010472 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0116] |
| GSM4010473 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0134] |
| GSM4010474 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0157] |
| GSM4010475 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0161] |
| GSM4010476 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0183] |
| GSM4010477 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0190] |
| GSM4010478 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0200] |
| GSM4010479 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0216] |
| GSM4010480 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0335] |
| GSM4010481 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0403] |
| GSM4010482 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0443] |
| GSM4010483 |
Placebo-arm, Poor outcome, Baseline [A_1_T0_DT0452] |
| GSM4010484 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0116] |
| GSM4010485 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0134] |
| GSM4010486 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0157] |
| GSM4010487 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0161] |
| GSM4010488 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0183] |
| GSM4010489 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0190] |
| GSM4010490 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0200] |
| GSM4010491 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0216] |
| GSM4010492 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0335] |
| GSM4010493 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0403] |
| GSM4010494 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0443] |
| GSM4010495 |
Placebo-arm, Poor outcome, 1 month post trichiasis surgery [A_1_T1_DT0452] |
| GSM4010496 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0016] |
| GSM4010497 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0133] |
| GSM4010498 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0318] |
| GSM4010499 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0326] |
| GSM4010500 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0374] |
| GSM4010501 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0405] |
| GSM4010502 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0549] |
| GSM4010503 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0613] |
| GSM4010504 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0625] |
| GSM4010505 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0646] |
| GSM4010506 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0670] |
| GSM4010507 |
Doxycycline-arm, Good outcome, Baseline [B_0_T0_DT0987] |
| GSM4010508 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0016] |
| GSM4010509 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0133] |
| GSM4010510 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0318] |
| GSM4010511 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0326] |
| GSM4010512 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0374] |
| GSM4010513 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0405] |
| GSM4010514 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0549] |
| GSM4010515 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0613] |
| GSM4010516 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0625] |
| GSM4010517 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0646] |
| GSM4010518 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0670] |
| GSM4010519 |
Doxycycline-arm, Good outcome, 1 month post trichiasis surgery [B_0_T1_DT0987] |
| GSM4010520 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0096] |
| GSM4010521 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0165] |
| GSM4010522 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0184] |
| GSM4010523 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0281] |
| GSM4010524 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0310] |
| GSM4010525 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0370] |
| GSM4010526 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0465] |
| GSM4010527 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0609] |
| GSM4010528 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0689] |
| GSM4010529 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0733] |
| GSM4010530 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0759] |
| GSM4010531 |
Doxycycline-arm, Poor outcome, Baseline [B_1_T0_DT0962] |
| GSM4010532 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0096] |
| GSM4010533 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0165] |
| GSM4010534 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0184] |
| GSM4010535 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0281] |
| GSM4010536 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0310] |
| GSM4010537 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0370] |
| GSM4010538 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0465] |
| GSM4010539 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0609] |
| GSM4010540 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0689] |
| GSM4010541 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0733] |
| GSM4010542 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0759] |
| GSM4010543 |
Doxycycline-arm, Poor outcome, 1 month post trichiasis surgery [B_1_T1_DT0962] |
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| Relations |
| BioProject |
PRJNA558960 |
| SRA |
SRP217543 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135455_Doxy_raw_read_count_matrix.xlsx |
9.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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