Predicting Transcript Production Rates in Yeast With Sparse Linear Models

To provide biological insights into transcriptional regulation, a couple of groups have recently presented models relating the promoter DNA-bound transcription factors (TFs) to downstream gene’s mean transcript level or transcript production rates over time. However, transcript production is dynamic in response to changes of TF concentrations over time. Also, TFs are not the only factors binding to promoters; other DNA binding factors (DBFs) bind as well, especially nucleosomes, resulting in competition between DBFs for binding at same genomic location. Additionally, not only TFs, but also some other elements regulate transcription. Within core promoter, various regulatory elements influence RNAPII recruitment, PIC formation, RNAPII searching for TSS, and RNAPII initiating transcription. Moreover, it is proposed that downstream from TSS, nucleosomes resist RNAPII elongation.

Here, we provide a machine learning framework to predict transcript production rates from DNA sequences. We applied this framework in the S. cerevisiae yeast for two scenarios: a) to predict the dynamic transcript production rate during the cell cycle for native promoters; b) to predict the mean transcript production rate over time for synthetic promoters. As far as we know, our framework is the first successful attempt to have a model that can predict dynamic transcript production rates from DNA sequences only: with cell cycle data set, we got Pearson correlation coefficient Cp = 0.751 and coefficient of determination r2 = 0.564 on test set for predicting dynamic transcript production rate over time. Also, for DREAM6 Gene Promoter Expression Prediction challenge, our fitted model outperformed all participant teams, best of all teams, and a model combining best team’s k-mer based sequence features and another paper’s biologically mechanistic features, in terms of all scoring metrics.

Moreover, our framework shows its capability of identifying generalizable fea- tures by interpreting the highly predictive models, and thereby provide support for associated hypothesized mechanisms about transcriptional regulation. With the learned sparse linear models, we got results supporting the following biological insights: a) TFs govern the probability of RNAPII recruitment and initiation possibly through interactions with PIC components and transcription cofactors; b) the core promoter amplifies the transcript production probably by influencing PIC formation, RNAPII recruitment, DNA melting, RNAPII searching for and selecting TSS, releasing RNAPII from general transcription factors, and thereby initiation; c) there is strong transcriptional synergy between TFs and core promoter elements; d) the regulatory elements within core promoter region are more than TATA box and nucleosome free region, suggesting the existence of still unidentified TAF-dependent and cofactor-dependent core promoter elements in yeast S. cerevisiae; e) nucleosome occupancy is helpful for representing +1 and -1 nucleosomes’ regulatory roles on transcription.

Bisphenol A alters transcript levels of biomarker genes for major depressive disorder in vascular endothelial cells and colon cancer cells

Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

HSP70 abundance and antioxidant capacity in feeding and fasting gray seal pups: suckling is associated with higher levels of key cellular defenses

Heat shock proteins (HSPs) and antioxidants are key cellular defenses against stress. Seals routinely undergo protracted fasting, which is normally associated with physiological stress in other animals. We tested the hypotheses that (1) relative HSP70 protein abundance is higher in liver and blubber of fasting relative to suckling wild gray seal pups; (2) differences in HSP70 are mirrored in tissue superoxide dismutase (SOD) and catalase activity, as well as glutathione levels; (3) extracellular HSP70 correlates with hepatic and blubber HSP70 abundance; and (4) protein carbonylation, an index of oxidative damage, is lower in tissues with higher levels of these cellular stress markers. In contrast to our expectation, suckling pups had higher relative HSP70 abundance and glutathione levels in liver and blubber and higher hepatic catalase activity. Plasma HSP70 did not correlate with liver or blubber abundance of the protein. Suckling pups did not experience greater protein carbonylation, suggesting that cellular protective mechanisms prevent protein damage despite an apparent increase in cellular stress. SOD activity was not affected by nutritional state, but in blubber tissue, it was positively correlated with blubber thickness. Greater requirements for antioxidants and HSPs in suckling pups or in animals with thicker blubber could arise from rapid protein synthesis, high metabolic fuel availability, and/or exposure to lipophilic toxins. Developmental and nutritional changes in cellular defenses have important implications for gray seals’ susceptibility to additional stress exposure.

Karl-Josef Pazzini / Marianne Schuller / Michael Wimmer (Hrsg.): Lehren bildet? Vom Rätsel unserer Lehranstalten Bielefeld: transcript 2010 [Rezension]

Rezension von: Karl-Josef Pazzini / Marianne Schuller / Michael Wimmer (Hrsg.): Lehren bildet? Vom Rätsel unserer Lehranstalten Bielefeld: transcript 2010 (338 S.; ISBN 978-3-8376-1176-2)

Eckart Liebau / Jörg Zirfas (Hrsg.): Die Bildung des Geschmacks, Über die Kunst der sinnlichen Unterscheidung. Bielefeld: transcript 2011 [Rezension]

Rezension von: Eckart Liebau / Jörg Zirfas (Hrsg.): Die Bildung des Geschmacks, Über die Kunst der sinnlichen Unterscheidung, Bielefeld: transcript 2011 228 S.; ISBN 978-3-8376-1746-7)

Kay Biesel: Wenn Jugendämter scheitern, Zum Umgang mit Fehlern im Kinderschutz. Bielefeld: transcript Verlag 2011 [Rezension]

Rezension von: Kay Biesel: Wenn Jugendämter scheitern, Zum Umgang mit Fehlern im Kinderschutz, Bielefeld: transcript Verlag 2011 (333 S.; ISBN 978-3-8376-1892-1)

Lisa Pfahl: Techniken der Behinderung, Der deutsche Lernbehindertendiskurs, die Sonderschule und ihre Auswirkungen auf Bildungsbiografien. Bielefeld: transcript 2011 [Rezension]

Rezension von: Lisa Pfahl: Techniken der Behinderung, Der deutsche Lernbehindertendiskurs, die Sonderschule und ihre Auswirkungen auf Bildungsbiografien, Bielefeld: transcript 2011 (276 S.; ISBN 978-3-8376-1532-6)

Transcript on the subject of the Bureau of Employment Agencies, and Assembly bill 3181 (Kapiloff), and Assembly bill 3297 (Sieroty) : public hearing on October 26, 1976, State Capitol, Room 4202, Sacramento, California /

Cover title.

Transcript of proceedings : collective bargaining /

At head of cover title: This is a rough draft.

Transcript of proceedings of the Arbitration Board (Arb. Bd. 192, N. M. B. case A-4400) : Chicago, Illinois, 1954. Wage increase case. Brotherhood of Locomotive Engineers vs. designated railroads.

On cover: Wage increase case.

Transcript of proceedings of Emergency Board No. 106, appointed by the President of the United States. Chicago, Illinois, 1954. Vacations, holidays, health and welfare benefits, rules. Fifteen cooperating railway labor organizations, vs. designated railroads.

Mode of access: Internet.

Civil service reform : development of 1978 civil service reform proposals : transcript of a seminar held jointly by GAO and the Senate Governmental Affairs Subcommittee on Federal Services, Post Office, and Civil Service on March 31, 1988 /

"GAO/GGD-89-18."

Peter Faulstich: Menschliches Lernen. Eine kritisch-pragmatistische Lerntheorie. Bielefeld: transcript 2013 (232 S.) [Rezension]

Rezension von: Peter Faulstich: Menschliches Lernen. Eine kritisch-pragmatistische Lerntheorie. Bielefeld: transcript 2013 (232 S.; ISBN 978-3-8376-2425-0)