Predicting Genetic Regulatory Response Using Classification

We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences (``motifs'') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment (``parents''). Thus our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurement to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S. cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks.Comment: 8 pages, 4 figures, presented at Twelfth International Conference on Intelligent Systems for Molecular Biology (ISMB 2004), supplemental website: http://www.cs.columbia.edu/compbio/geneclas

Hidden Treasure: Connecting Your Value with the Needs of the Institution

While traditionally libraries are very good at counting (books, patrons, reference questions, etc.), the question of value can no longer be answered by quantifying things and activities. In fact, it is challenging to try to assess and assign value to the services and resources provided by libraries. Increasingly libraries are asked to communicate their value to their stakeholders more effectively by providing evidence of outcomes related to user experience and institutional mission and goals. Several library associations have recently published reports delineating the value of libraries to the constituents

Telling Your Story: Articulating Your Value as a Technical Services Librarians

If you can translate your skills and achievements so others see their value and impact, everyone wins. Whether justifying the need to fill an open position, writing a tenure or promotion narrative, or even carrying on a conversation with a colleague, librarians who work in Technical Services are often challenged to articulate what they do and the value it brings to the institution they serve. In this webinar we will discuss: The challenge of defining value in the context of technical services Assessment measures that determine the impact of technical services “products” on users Connecting the impact of technical services to the mission of the institution Developing a 30-second elevator speech to explain the value of technical services to those outside the librar

Vocabulary Development in Greek Children: A Cross-Linguistic Comparison Using the Language Development Survey

This study investigated vocabulary size and vocabulary composition in Greek children aged 1; 6 to 2; 11 using a Greek adaptation of Rescorla\u27s Language Development Survey (LDS; Rescorla, 1989). Participants were 273 toddlers coming from monolingual Greek-speaking families. Greek LDS data were compared with US LDS data obtained from the instrument\u27s normative sample (Achenbach & Rescorla, 2000). Vocabulary size increased markedly with age, but Greek toddlers appeared to get off to a slower start in early word learning than US children. The correlation between percentage word use scores in Greek and US samples was moderate in size, indicating considerable overlap but some differences. Common nouns were the largest category among the fifty most frequent words in both samples. Numbers of adjectives and verbs were comparable across languages, but people and closed-class words were more numerous in the Greek sample. Finally, Greek late talkers showed similar patterns of vocabulary composition to those observed in typically developing Greek children

Campus & alumni news

Boston University Medicine was published by the Boston University Medical Campus, and presented stories on events and topics of interest to members of the BU Medical Campus community. It followed the discontinued publication Centerscope as Boston University Medicine from 1991-2005, then continued as Campus & Alumni News from 2006-2013 before returning to the title Boston University Medicine from 2014-present

Essential Roles for Mycobacterium tuberculosis Rel beyond the Production of (p)ppGpp

In Mycobacterium tuberculosis, the stringent response to amino acid starvation is mediated by the M. tuberculosis Rel (Rel(Mtb)) enzyme, which transfers a pyrophosphate from ATP to GDP or GTP to synthesize ppGpp and pppGpp, respectively. (p)ppGpp then influences numerous metabolic processes. Rel(Mtb) also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into pyrophosphate and GDP or GTP. Rel(Mtb) is required for chronic M. tuberculosis infection in mice; however, it is unknown which catalytic activity of Rel(Mtb) mediates pathogenesis and whether (p)ppGpp itself is necessary. In order to individually investigate the roles of (p)ppGpp synthesis and hydrolysis during M. tuberculosis pathogenesis, we generated Rel(Mtb) point mutants that were either synthetase dead (Rel(Mtb)(H344Y)) or hydrolase dead (Rel(Mtb)(H80A)). M. tuberculosis strains expressing the synthetase-dead Rel(Mtb)(H344Y) mutant did not persist in mice, demonstrating that the Rel(Mtb) (p)ppGpp synthetase activity is required for maintaining bacterial titers during chronic infection. Deletion of a second predicted (p)ppGpp synthetase had no effect on pathogenesis, demonstrating that Rel(Mtb) was the major contributor to (p)ppGpp production during infection. Interestingly, expression of an allele encoding the hydrolase-dead Rel(Mtb) mutant, Rel(Mtb)(H80A), that is incapable of hydrolyzing (p)ppGpp but still able to synthesize (p)ppGpp decreased the growth rate of M. tuberculosis and changed the colony morphology of the bacteria. In addition, Rel(Mtb)(H80A) expression during acute or chronic M. tuberculosis infection in mice was lethal to the infecting bacteria. These findings highlight a distinct role for Rel(Mtb)-mediated (p)ppGpp hydrolysis that is essential for M. tuberculosis pathogenesis

The DNA Triangle and Its Application to Learning Meiosis

Although instruction on meiosis is repeated many times during the undergraduate curriculum, many students show poor comprehension even as upper-level biology majors. We propose that the difficulty lies in the complexity of understanding DNA, which we explain through a new model, the DNA triangle. The DNA triangle integrates three distinct scales at which one can think about DNA: chromosomal, molecular, and informational. Through analysis of interview and survey data from biology faculty and students through the lens of the DNA triangle, we illustrate important differences in how novices and experts are able to explain the concepts of ploidy, homology, and mechanism of homologous pairing. Similarly, analysis of passages from 16 different biology textbooks shows a large divide between introductory and advanced material, with introductory books omitting explanations of meiosis-linked concepts at the molecular level of DNA. Finally, backed by textbook findings and feedback from biology experts, we show that the DNA triangle can be applied to teaching and learning meiosis. By applying the DNA triangle to topics on meiosis we present a new framework for educators and researchers that ties concepts of ploidy, homology, and mechanism of homologous pairing to knowledge about DNA on the chromosomal, molecular, and informational levels

Students Fail to Transfer Knowledge of Chromosome Structure to Topics Pertaining to Cell Division

Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and in-depth interviews under the theory of knowledge transfer to explain student difficulties with concepts related to chromosomal behavior. In this paper, we show that students typically understand basic chromosome structure but do not activate cognitive resources that would allow them to explain macromolecular phenomena (e.g., homologous pairing during meiosis). To improve understanding of topics related to genetic information flow, we suggest that instructors use pedagogies and activities that prime students for making connections between chromosome structure and cellular processes

Acoustic enhancement of intracellular delivery for ex vivo therapeutics

Recent advances in gene editing and therapy have highlighted the potential of ex vivo cell-based techniques to treat many diseases, wherein a patient’s cells are harvested, engineered to insert various therapeutic agents such as nucleic acids or proteins, and re-infused. Considerable challenges however remain in the ability not just to insert these agents into cells whilst retaining high levels of cellular viability, but also to ensure that they are not lysed within the cell. Please click Additional Files below to see the full abstract