Fairness-Aware Ranking in Search & Recommendation Systems with Application to LinkedIn Talent Search

We present a framework for quantifying and mitigating algorithmic bias in mechanisms designed for ranking individuals, typically used as part of web-scale search and recommendation systems. We first propose complementary measures to quantify bias with respect to protected attributes such as gender and age. We then present algorithms for computing fairness-aware re-ranking of results. For a given search or recommendation task, our algorithms seek to achieve a desired distribution of top ranked results with respect to one or more protected attributes. We show that such a framework can be tailored to achieve fairness criteria such as equality of opportunity and demographic parity depending on the choice of the desired distribution. We evaluate the proposed algorithms via extensive simulations over different parameter choices, and study the effect of fairness-aware ranking on both bias and utility measures. We finally present the online A/B testing results from applying our framework towards representative ranking in LinkedIn Talent Search, and discuss the lessons learned in practice. Our approach resulted in tremendous improvement in the fairness metrics (nearly three fold increase in the number of search queries with representative results) without affecting the business metrics, which paved the way for deployment to 100% of LinkedIn Recruiter users worldwide. Ours is the first large-scale deployed framework for ensuring fairness in the hiring domain, with the potential positive impact for more than 630M LinkedIn members.Comment: This paper has been accepted for publication at ACM KDD 201

Tay Bridge Is a Negative Regulator of EGFR Signalling and Interacts with Erk and Mkp3 in theDrosophila melanogaster Wing

The regulation of Extracellular regulated kinase (Erk) activity is a key aspect of signalling by pathways activated by extracellular ligands acting through tyrosine kinase transmembrane receptors. In this process, participate proteins with kinase activity that phosphorylate and activate Erk, as well as different phosphatases that inactivate Erk by de-phosphorylation. The state of Erk phosphorylation affects not only its activity, but also its subcellular localization, defining the repertoire of Erk target proteins, and consequently, the cellular response to Erk. In this work, we characterise Tay bridge as a novel component of the EGFR/Erk signalling pathway. Tay bridge is a large nuclear protein with a domain of homology with human AUTS2, and was previously identified due to the neuronal phenotypes displayed by loss-of-function mutations. We show that Tay bridge antagonizes EGFR signalling in the Drosophila melanogaster wing disc and other tissues, and that the protein interacts with both Erk and Mkp3. We suggest that Tay bridge constitutes a novel element involved in the regulation of Erk activity, acting as a nuclear docking for Erk that retains this protein in an inactive form in the nucleus. © 2013 Molnar, de Celis.BFU2009-09403; BFU2012-33994; CSD2007-00008; Fundación Ramón ArecesPeer Reviewe

Linking pseudouridine synthases to growth, developmentand cell competition

Eukaryotic pseudouridine synthases direct RNA pseudouridylation and bind H⁄ACA small nucleolar RNA (snoRNAs), which, in turn, may act as precursors of microRNA-like molecules. In humans, loss of pseudouridine synthase activity causes dyskeratosis congenita (DC), a complex systemic disorder characterized by cancer susceptibility, failures in ribosome biogenesis and telomere stability, and defects in stem cell formation. Considering the significant interest in deciphering the various molecular consequences of pseudouridine synthase failure, we performed a loss of function analysis of minifly (mfl), the pseudouridine synthase gene of Drosophila, in the wing disc, an advantageous model system for studies of cell growth and differentiation. In this organ, depletion of the mfl-encoded pseudouridine synthase causes a severe reduction in size by decreasing both the number and the size of wing cells. Reduction of cell number was mainly attributable to cell death rather than reduced proliferation, establishing that apoptosis plays a key role in the development of the loss of function mutant phenotype. Depletion of Mfl also causes a proliferative disadvantage in mosaic tissues that leads to the elimination of mutant cells by cell competition. Intriguingly, mfl silencing also triggered unexpected effects on wing patterning and cell differentiation, including deviations from normal lineage boundaries, mingling of cells of different compartments, and defects in the formation of the wing margin that closely mimic the phenotype of reduced Notch activity. These results suggest that a component of the pseudouridine synthase loss of function phenotype is caused by defects in Notch signalling

The balance between GMD and OFUT1 regulates notch signaling pathway activity by modulating notch stability

The Notch signaling pathway plays an important role in development and physiology. In Drosophila, Notch is activated by its Delta or Serrate ligands, depending in part on the sugar modifications present in its extracellular domain. O-fucosyltransferase-1 (OFUT1) performs the first glycosylation step in this process, O-fucosylating various EGF repeats at the Notch extracellular domain. Besides its O-fucosyltransferase activity, OFUT1 also behaves as a chaperone during Notch synthesis and is able to down regulate Notch by enhancing its endocytosis and degradation. We have reevaluated the roles that O-fucosylation and the synthesis of GDP-fucose play in the regulation of Notch protein stability. Using mutants and the UAS/Gal4 system, we modified in developing tissues the amount of GDP-mannosedeshydratase (GMD), the first enzyme in the synthesis of GDP-fucose. Our results show that GMD activity, and likely the levels of GDPfucose and O-fucosylation, are essential to stabilize the Notch protein. Notch degradation observed under low GMD expression is absolutely dependent on OFUT1 and this is also observed in Notch Abruptex mutants, which have mutations in some potential O-fucosylated EGF domains. We propose that the GDP-fucose/OFUT1 balance determines the ability of OFUT1 to endocytose and degrade Notch in a manner that is independent of the residues affected by Abruptex mutations in Notch EGF domains.This work was funded by ICM P06-039F grant to A.G. and by a BFU2009-09403 grant of the M.E.C. to J.F.dC. An institutional grant from the Ramón Areces Foundation to the CBMSO is also acknowledged.Peer Reviewe

High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier.

Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, and their effects on Pol II nucleosome crossing dynamics, is still missing. Here, we obtain topographic and transcriptional (Pol II residence time) maps of canonical, H2A.Z, and monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution and accuracy. Pol II crossing dynamics are complex, displaying pauses at specific loci, backtracking, and nucleosome hopping between wrapped states. While H2A.Z widens the barrier, uH2B heightens it, and both modifications greatly lengthen Pol II crossing time. Using the dwell times of Pol II at each nucleosomal position we extract the energetics of the barrier. The orthogonal barrier modifications of H2A.Z and uH2B, and their effects on Pol II dynamics rationalize their observed enrichment in +1 nucleosomes and suggest a mechanism for selective control of gene expression

Drosophila as a model system for genetic and genomic research

The sequencing of the Drosophila genome allowed the identification of most coding sequences, highlighting the necessity for a functional assignation of the identified genes. The information extracted from the sequence directly classified a considerable fraction of genes into known molecular categories, although there is still a large proportion of them that, due to poor sequence conservation, are not included into any informative class. Furthermore, in many instances the molecular nature of a protein is not particularly revealing about its functional requirements and network of interactions. In this manner, complementary genomic approaches to gene identification by sequence conservation are fundamental both in Drosophila and other organisms to assign particular functions to annotated genes. The approach more successful in the Drosophila field is the undertaking of genetic screenings to identify sets of interacting genes and genes controlling particular cellular processes. Classic genetic screens comprise all those based on a “phenotypic” paradigm, where the generation of large collections of mutant chromosomes is followed by their mapping. This approach has been recently expanded to include “genomic” tools, such as the use of microarrays and interference RNA, as well as reverse-genetics techniques, seeding the way to a “functional” annotation of the Drosophila genome.Peer reviewe

Qualitative risk assessment of animal meal applied to swine production

There are gaps in the pig production chain, particularly as regards the possible destinations of dead animals on farms. The production of animal meal presents itself as an alternative for the recycling of biological waste. The objective of this study was realize a qualitative microbiological risk assessment on animal meal in order to provide subsidies to indicate possible hazards and risks associated with the use of meal produced from dead pigs on farms. The microorganism Salmonella was the main hazard reported. The scenario tree presented 15 scenarios for contamination and recontamination of animal meal. For the first scenario was defined release and exposure risk levels as moderate, was obtained as the risk level of the occurrence moderate. The risk level of the consequence determined as low together with the level of occurrence obtained previously resulted in the final risk level low. For the second scenario defined release risk level as high and the exposure risk level as moderate, we obtained as moderate risk level of occurrence. The risk level of the consequence determined as high related to the level of occurrence previously obtained resulted in the final risk level high. From the information and scenarios considered, it was not possible to indicate the production of animal meal as a probable destination for dead animals on pig farms