About BAGIM

BAGIM is an active community of Boston area scientists bringing together people from diverse fields of modeling and informatics to impact life and health sciences. BAGIM strives to create a forum for great scientific discussions covering a wide range of topics including data management, visualization, computational chemistry, drug discovery, protein structure, molecular modeling, structure-based drug design, data mining, software tools, and the sharing of goals and experiences. Our community is made up of participants from academia, government, and industry whose goal is to engage in the discussion of science involving a synthesis of theory and technology. Discussions sponsored by BAGIM are targeted to the needs and interests of informatics scientists, computational chemists, medicinal chemists, and statisticians. BAGIM also provides opportunities for networking within these disciplines as well as an arena for the dissemination of information of specific interest to the membership.

Tuesday, November 13, 2018

BAGIM Event: Anne Carpenter, Ph.D.

Anne Carpenter will present on "Accelerating drug discovery through the power of microscopy images."

Microscopy images contain tremendous information about the state of cells, tissues, and organisms. We work with biomedical researchers around the world to extract metrics from cell images, particularly in high-throughput screening experiments testing drugs in disease model systems. As the cell systems and phenotypes of interest become more complex, so are the computational approaches needed to properly extract the information of interest; we continue to bridge the gap between biologists’ needs, such as 3D organoid models, and the latest in computational science, such as deep learning algorithms.

Beyond measuring features that biologists specify, we extract even more from images through profiling experiments using the Cell Painting assay, where thousands of morphological features are measured from each cell’s image. We are working to harvest similarities in these “profiles” for identifying how drugs and genes affect cells, identifying the functional impact of cancer-associated alleles, discovering disease-associated phenotypes, and identifying novel therapeutics. Ultimately, we aim to make perturbations in cell morphology as computable as genomics data.

All novel algorithms and approaches from our laboratory are released as open-source software, including CellProfiler, CellProfiler Analyst, and cytominer.

Anne Carpenter is senior director of the Imaging Platform at Broad Institute of MIT and Harvard. Carpenter is now a pioneer in image-based profiling, the extraction of rich, unbiased information from images for drug discovery, and functional genomics. She collaborates with dozens of biomedical research groups around the world to develop and apply image analysis methods to diverse biological questions. Carpenter is an NIH MIRA investigator, an NSF CAREER awardee, and has received recognition and research funding from numerous other groups including the Human Frontiers in Science program and the Howard Hughes Medical Institute. Carpenter earned her B.S. from Purdue University and her Ph.D. from the University of Illinois at Urbana-Champaign.

Please follow her on twitter: @DrAnneCarpenter

Thursday, October 4, 2018

BAGIM Event: Derek Lowe on October 18th at 6pm at Le Meridien

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He’s worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer’s, diabetes, osteoporosis and other diseases. Derek is the author of the widely read "In the Pipeline" blog.

http://blogs.sciencemag.org/pipeline/


Thursday, September 13, 2018

First BAGIM event of the season: Roy Vaz

Title: A data analysis exercise to decipher kinase antitargets

Roy J. Vaz received his Ph.D. from the University of Florida, Gainesville in Chemistry with Profs. G. B. Butler and M. Zerner. He obtained an undergraduate degree from the Indian Institute of Technology, Bombay. After his Ph.D., he obtained an MBA from the University of Illinois, UC and most recently an MS in Molecular Biology from Lehigh University. He was responsible for managing the CADD, SB and Cheminformatics efforts at Sanofi, Bridgewater, NJ prior to relocating and supporting small molecule discovery at Sanofi-Genzyme, Waltham, MA. He was previously Director of the Investigative Product Optimization department at Aventis in Bridgewater. He has worked with Bristol-Myers Squibb, Hopewell as Principal Scientist as well as Tripos, Inc, St. Louis as a Research Scientist. He has authored or co-authored over 50 publications in peer-reviewed journals, contributed towards many book chapter and several patents and edited 2 books related to Antitargets.

Wednesday, August 8, 2018

Illuminating the Druggable Genome (IDG) Outreach with BAGIM

IDG Outreach meeting with BAGIM
9 am – 2 pm, August 23, 2018
Harvard Medical School
Boston, MA

RSVP Email: idg.rdoc@gmail.com before August 19th, or you will not be able to enter the building.
Come and hear more about Illuminating the Druggable Genome Consortium, a NIH Common Fund program,
composed of Knowledge Management Centers (KMC), Data Resource Generating Centers (DRGC), and
Resource Dissemination and Outreach Center (RDOC).

Agenda:

9:00 Welcome and Introduction - Tudor Oprea, PhD, MD

9:05 Presentation from KMC at University of New Mexico (UNM)
Protein Knowledge Graphs and Machine Learning for
Target Prioritization - Tudor Oprea, PhD, MD

9:30 Presentation from KMC at Icahn School of Medicine at Mt.
Sinai (ISMMS)
Harmonizome-ML: Interactive On-the-Fly Imputation of
Knowledge about Genes and Proteins with Machine
Learning - Avi Ma'ayan, PhD

9:55 Presentation from KMC at National Center for Advancing
Translational Sciences (NCATS)
Pharos, User-Interface to Illuminating Druggable Genome -
Dac-Trung Nguyen and Timothy Sheils

10:20 Break

10:35 Presentation from DRGC - Kinase
Dark Kinase Knowledgebase - Matthew Berginski, PhD
(UNC at Chapel Hill)
Small Molecule Library Informatics - Nienki Moret, Bsc
(Harvard)

11:25 Presentation from DRGC - Ion Channel
Data driven co-ablation of Ion Channels - Zicheng Hu, PhD
(UCSF)

11:50 Break

12:20 Presentation from outside IDG community
Functional and structural interactions in druggable targets
from evolutionary information - Chris Sander, PhD
(Harvard)
Genetic variation in human drug-related genes - Debora
Marks, PhD (Harvard)

13:10 Feedback loop: Discussion on improvements to better
serve the community.

Location:
Harvard Medical School
Warren Alpert Building, Room 563
200 Longwood Avenue
Boston, MA 02115

**Attendees**: Please email your name and affiliation to idg.rdoc@gmail.com by August 19, 2018 in order to

pass HMS building security.
BAGIM - Boston Area Group for Informatics and Modeling

DruggableGenome.net

Friday, December 15, 2017

BAGIM Event: Dr. Douglas Selinger at Merck in Boston Thursday Jan 11 2018 starting at 6pm

Dr. Douglas Selinger, CEO of Plex Research, will present "A search for cures: Chemical biology data analysis using search algorithms" on January 11th, 2018. The presentation will start at 6pm at the Merck Research Laboratories at 33 Avenue Louis Pasteur in Boston. Please arrive a few minutes early. Networking and refreshments will be after the talk in the same location.

Please RSVP for this meeting

Abstract

We can find web sites. We can find restaurant reviews. Yet our scientific data and algorithms are buried in databases and spread across incompatible sources. Why not build a search engine for science?

Search engine algorithms, originally designed to make sense of interconnected web pages, can be repurposed to analyze linked data of all kinds. At Plex we’ve developed a search engine which incorporates chemical similarity (e.g. 2D/3D fingerprints), biological fingerprints (e.g. transcriptional profiling), and machine learning approaches. We’ve pointed this engine at a large corpus of publicly available data, including: compounds, targets, pathways, biomarkers, ADME, toxicity, diseases, patents, publications, and more. The results are powerful, yet simple.

Come join us to learn more as we explore the uses of search engine algorithms in drug discovery.


BAGIM is sponsored by Accenture, Dassault Systemes, DNASTAR, OpenEye Scientific, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Dotmatics, Cresset, Cyrus Biotechnology, Optibrium, Team Arrayo, and Scilligence

Wednesday, October 18, 2017

BAGIM Event: Dr Gabriel Musso at the Broad Institute in Cambridge Thursday November 16, starting at 6pm

Dr. Gabriel Musso, the CSO of BioSymetrics in Toronto, will present "Using Machine Learning to Screen Small Molecules" on November 16th. The presentation will start at 6pm at the Broad Institute. Please use the 415 Main Street entrance and arrive a few minutes early. Networking and refreshments will follow at around 7pm at Meadhall, 4 Cambridge Center, Cambridge. Please RSVP for this event.

Abstract

Drug discovery in the post-genomic era has largely focused on modulation of disease-relevant drug targets in hypothesis-driven screens. However, despite tremendous achievements, there is substantial pressure within the industry to address the high attrition rate associated with drug development. Failures in the clinical development of lead compounds may arise from lack of efficacy, unexpected toxicity, or anomalies in absorption, distribution, metabolism, or excretion. One potential solution to this problem is to incorporate an initial phenotype-based screen able to assess multiple specificity and toxicity phenotypes simultaneously. In this talk I’ll begin by describing previous work in which we performed phenotype-based screening of a library of bioactive compounds, using the results to generate machine learning models that prioritized as-yet-untested compounds for specific phenotypic effects. These models were used to generate nearly 700 million predicted structure-activity relationships, and highlight a mechanism-agnostic means for combined in vivo and in silico screening of massive chemical libraries. Our current goal is to design an informatics suite that would produce more advanced small molecule activity predictions by incorporating experimental data from multiple sources. We feel this approach has the ability to disrupt traditional lead compound discovery frameworks.

BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, OpenEye Scientific, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Dotmatics, Cresset, Cyrus Biotechnology, Optibrium, Team Arrayo, and Scilligence

Thursday, September 14, 2017

BAGIM Event: Dr. Heidi Koldsø at Moderna in Cambridge, Thursday Oct 19th

Dr. Heidi Koldsø from D. E. Shaw Research will present "Permeation, gating, and modulation of the TRPA1 channel in long-timescale molecular dynamics simulations"on Thursday, October 19, 2017.  The talk will be held at Moderna Therapeutics at 200 Technology Square in Cambridge, starting at 6pm.  Please plan to arrive ten to fifteen minutes before the start.  Networking and refreshments will follow the talk at Meadhall, 4 Cambridge Center. 

TRPA1, a member of the transient receptor potential (TRP) ion channel superfamily, is a nonspecific cation channel activated by natural chemicals found in, for instance, mustard, oregano, and cinnamon.  TRPA1 has recently appeared as a promising drug target in pain and inflammatory diseases.  Structure-based design efforts for this protein are problematic, however, due to the lack of molecular details of relevant channel functional states and of channel activation. 


To address this problem, we have studied TRPA1 channel functional states and channel activation using long-timescale, all-atom molecular dynamics simulations enabled by special-purpose hardware.  Specifically, we simulated inward and outward ionic currents, which helped us identify possible key structural determinants of channel gating.  We also studied modulation of the open and conducting channel by performing simulations of free binding of the TRPA1 inhibitor A-967079 to TRPA1.  Intriguingly, A-967079 was observed to bind in a location previously hypothesized to be a binding site.  Our observations suggest that this site may indeed be a target for development of new allosteric modulators, an avenue we intend to explore in the future.

Heidi Koldsø is a member of the technical team at D. E. Shaw Research, a company that develops specialized hardware and software for basic and applied computational biochemical research. She holds a Ph.D. in chemistry from Aarhus University in Denmark, as well as a M.Sc. and B.Sc. in Medicinal Chemistry, also from Aarhus University. After her Ph.D., she was a postdoctoral researcher at the Department of Biochemistry, University of Oxford. At D. E. Shaw Research, she applies molecular dynamics simulations to study biological systems, with a focus on ion channels.

BAGIM is sponsored by Dassault Systemes, DNASTAR, LabAnswer, OpenEye Scientific, Schrodinger, Silicon Therapeutics, Acellera, Acpharis, Cambridge Crystallographic Data Centre, Chemical Computing Group, Dotmatics, Cresset, Cyrus Biotechnology, Optibrium, Team Arrayo, and Scilligence