Target identification strategies in plant chemical biology

The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starting blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, whereas studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology

Therapeutic target discovery using Boolean network attractors: avoiding pathological phenotypes

Target identification, one of the steps of drug discovery, aims at identifying biomolecules whose function should be therapeutically altered in order to cure the considered pathology. This work proposes an algorithm for in silico target identification using Boolean network attractors. It assumes that attractors of dynamical systems, such as Boolean networks, correspond to phenotypes produced by the modeled biological system. Under this assumption, and given a Boolean network modeling a pathophysiology, the algorithm identifies target combinations able to remove attractors associated with pathological phenotypes. It is tested on a Boolean model of the mammalian cell cycle bearing a constitutive inactivation of the retinoblastoma protein, as seen in cancers, and its applications are illustrated on a Boolean model of Fanconi anemia. The results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice, thus requiring it to be used in combination with wet lab experiments. Nevertheless, it is expected that the algorithm is of interest for target identification, notably by exploiting the inexpensiveness and predictive power of computational approaches to optimize the efficiency of costly wet lab experiments.Comment: Since the publication of this article and among the possible improvements mentioned in the Conclusion, two improvements have been done: extending the algorithm for multivalued logic and considering the basins of attraction of the pathological attractors for selecting the therapeutic bullet

Target Type Identification for Entity-Bearing Queries

Identifying the target types of entity-bearing queries can help improve retrieval performance as well as the overall search experience. In this work, we address the problem of automatically detecting the target types of a query with respect to a type taxonomy. We propose a supervised learning approach with a rich variety of features. Using a purpose-built test collection, we show that our approach outperforms existing methods by a remarkable margin. This is an extended version of the article published with the same title in the Proceedings of SIGIR'17.Comment: Extended version of SIGIR'17 short paper, 5 page

Control through operators for quantum chemistry

We consider the problem of operator identification in quantum control. The free Hamiltonian and the dipole moment are searched such that a given target state is reached at a given time. A local existence result is obtained. As a by-product, our works reveals necessary conditions on the laser field to make the identification feasible. In the last part of this work, some algorithms are proposed to compute effectively these operators

Rapid creation and quantitative monitoring of high coverage shRNA libraries.

Short hairpin RNA libraries are limited by low efficacy of many shRNAs and by off-target effects, which give rise to false negatives and false positives, respectively. Here we present a strategy for rapidly creating expanded shRNA pools (approximately 30 shRNAs per gene) that are analyzed by deep sequencing (EXPAND). This approach enables identification of multiple effective target-specific shRNAs from a complex pool, allowing a rigorous statistical evaluation of true hits

Deep Memory Networks for Attitude Identification

We consider the task of identifying attitudes towards a given set of entities from text. Conventionally, this task is decomposed into two separate subtasks: target detection that identifies whether each entity is mentioned in the text, either explicitly or implicitly, and polarity classification that classifies the exact sentiment towards an identified entity (the target) into positive, negative, or neutral. Instead, we show that attitude identification can be solved with an end-to-end machine learning architecture, in which the two subtasks are interleaved by a deep memory network. In this way, signals produced in target detection provide clues for polarity classification, and reversely, the predicted polarity provides feedback to the identification of targets. Moreover, the treatments for the set of targets also influence each other -- the learned representations may share the same semantics for some targets but vary for others. The proposed deep memory network, the AttNet, outperforms methods that do not consider the interactions between the subtasks or those among the targets, including conventional machine learning methods and the state-of-the-art deep learning models.Comment: Accepted to WSDM'1