Using transcriptomics to guide lead optimization in drug discovery projects : lessons learned from the QSTAR project

The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making

A Fast Causal Profiler for Task Parallel Programs

This paper proposes TASKPROF, a profiler that identifies parallelism bottlenecks in task parallel programs. It leverages the structure of a task parallel execution to perform fine-grained attribution of work to various parts of the program. TASKPROF's use of hardware performance counters to perform fine-grained measurements minimizes perturbation. TASKPROF's profile execution runs in parallel using multi-cores. TASKPROF's causal profile enables users to estimate improvements in parallelism when a region of code is optimized even when concrete optimizations are not yet known. We have used TASKPROF to isolate parallelism bottlenecks in twenty three applications that use the Intel Threading Building Blocks library. We have designed parallelization techniques in five applications to in- crease parallelism by an order of magnitude using TASKPROF. Our user study indicates that developers are able to isolate performance bottlenecks with ease using TASKPROF.Comment: 11 page

Coz: Finding Code that Counts with Causal Profiling

Improving performance is a central concern for software developers. To locate optimization opportunities, developers rely on software profilers. However, these profilers only report where programs spent their time: optimizing that code may have no impact on performance. Past profilers thus both waste developer time and make it difficult for them to uncover significant optimization opportunities. This paper introduces causal profiling. Unlike past profiling approaches, causal profiling indicates exactly where programmers should focus their optimization efforts, and quantifies their potential impact. Causal profiling works by running performance experiments during program execution. Each experiment calculates the impact of any potential optimization by virtually speeding up code: inserting pauses that slow down all other code running concurrently. The key insight is that this slowdown has the same relative effect as running that line faster, thus "virtually" speeding it up. We present Coz, a causal profiler, which we evaluate on a range of highly-tuned applications: Memcached, SQLite, and the PARSEC benchmark suite. Coz identifies previously unknown optimization opportunities that are both significant and targeted. Guided by Coz, we improve the performance of Memcached by 9%, SQLite by 25%, and accelerate six PARSEC applications by as much as 68%; in most cases, these optimizations involve modifying under 10 lines of code.Comment: Published at SOSP 2015 (Best Paper Award

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Elephant Search with Deep Learning for Microarray Data Analysis

Even though there is a plethora of research in Microarray gene expression data analysis, still, it poses challenges for researchers to effectively and efficiently analyze the large yet complex expression of genes. The feature (gene) selection method is of paramount importance for understanding the differences in biological and non-biological variation between samples. In order to address this problem, a novel elephant search (ES) based optimization is proposed to select best gene expressions from the large volume of microarray data. Further, a promising machine learning method is envisioned to leverage such high dimensional and complex microarray dataset for extracting hidden patterns inside to make a meaningful prediction and most accurate classification. In particular, stochastic gradient descent based Deep learning (DL) with softmax activation function is then used on the reduced features (genes) for better classification of different samples according to their gene expression levels. The experiments are carried out on nine most popular Cancer microarray gene selection datasets, obtained from UCI machine learning repository. The empirical results obtained by the proposed elephant search based deep learning (ESDL) approach are compared with most recent published article for its suitability in future Bioinformatics research.Comment: 12 pages, 5 Tabl