ASCACBERAC Joint Panel on Accelerating Progress Toward GTL Goals

1
ASCAC-BERAC Joint Panel on Accelerating Progress
Toward GTL Goals

• Some concerns that were expressed by ASCAC members

2
Summary of Concerns

• Growing Divergence Between ASCR and BER goals
• Current BERAC definitions create a very high risk
  of failure
• Lack of clarity with regard to program
  responsibilities
• Lack of prioritization for resource constrained
  scenarios
• Lack of intermediate goals that would provide
  true indicators of success/concern
• Need for a follow-up study

3
Growing Divergence Between ASCR and BER goals

• (2008) The ten-year OMB PART goal for ASCR for
  the joint modeling and simulation activity of
  ASCR and BER should be modified to read as
  follows
• (ASCR) By 2018, demonstrate significant advances
  in the capability to predict an organisms
  phenotype from its genome sequence, through
  advances in genome sequence annotation, whole
  genome modeling and simulation, and integrated
  model-driven experimentation.
• (2006) BERAC proposes the following as a
  replacement for the Life Sciences PART measure
• By 2015, provide sufficient scientific
  understanding of plants and microbes to develop
  robust new strategies to produce biofuels, clean
  up waste, or sequester carbon. This includes
  research that supports the development of
  computational models to direct the use and design
  of improved organisms carrying out these
  processes.

4
Current BERAC definitions create a very high
risk of failure

• (2006) BERAC proposes the following grading
  scale for the revised PART measure
• Excellent Systems biology understanding and
  computational models that accurately describe the
  capabilities and potential of key processes in
  microbes, microbial communities, or plants for
  production of biofuels, to clean up waste, or to
  sequester carbon are developed and validated
  experimentally by the use or reengineering of
  those microbes, microbial communities or plants
  based on model predictions.
• Good Systems biology understanding and
  computational models that accurately describe the
  potential of key microbes, microbial communities,
  or plants for production of biofuels, to clean up
  waste, or to sequester carbon are developed and
  validated by their consistency with available
  data.
• Fair Systems biology understanding and
  computational models that describe the potential
  of key microbes, microbial communities or plants
  for production of biofuels, to clean up waste, or
  to sequester carbon are developed but are not yet
  validated.
• Poor Systems biology understanding of the
  potential of key microbes, microbial communities
  or plants for production of biofuels, to clean up
  waste, or to sequester carbon is developed but
  robust computational models describing these
  systems are not developed.
• BER automatically gets Poor without ASCR and
  suggested revision of ASCR goal generates a
  disconnect that may result in failure for both
  programs.

5
Lack of clarity with regard to program
responsibilities

• Recommendation 5, is notable for identifying the
  roles of each program. This should be explicitly
  included in all of the recommendations.
• Recommendation 5. DOE should establish a
  mechanism to support the long-term curation and
  integration of genomics and related datasets
  (annotations, metabolic reconstructions,
  expression data, whole genome screens, phenotype
  data, etc.) to support biological research in
  general and specifically the needs of modeling
  and simulation in particular in areas of energy
  and the environment that are not well supported
  by NSF and NIH.
• This mechanism should target the creation of a
  state-of-the-art community resource for data of
  all forms that are relevant to organisms of
  interest to DOE. This should be a joint activity
  of ASCR and BER, with ASCR responsible for the
  database and computational infrastructure to
  enable community annotation and data sharing. It
  should also leverage the work of established
  groups.

6
Lack of prioritization for resource constrained
scenarios

• The report needs to provide an order of magnitude
  for a funding envelope for appropriate scale
  and should identify priorities in the face of
  almost certain resource constraints.
• ASCAC discussion regarding the ASCR portfolio
  indicated that the ASCR resources available for
  this effort (2M in FY08) will not grow
  significantly in the goal time horizon.
• BER resources directly relevant to this effort
  are higher but the same order of magnitude
  (5M).

7
Lack of intermediate goals that would provide
true indicators of success/concern

• The report identified two general areas for
  intermediate goals but these are, as a set,
  neither necessary nor sufficient to assess
  progress, or lack of progress, toward the goal.
• Intermediate goals that could be considered more
  relevant for the two programs fall into two
  general areas.
• The first area is building needed tools, curated
  databases, and computational and collaborative
  infrastructure that directly support accelerating
  the communities ability to develop models and
  simulations. Examples of these are tools for
  curation of genomes and reconstruction of
  metabolic networks, integrated databases enabling
  the community to share data needed to build and
  test models and validation datasets, and
  mathematical libraries and core model components
  that would enable many groups to leverage the
  work of others.
• The second area is focusing on a targeted set of
  biological modeling and simulations problems that
  build on each other and that over time would
  expand the modeling capabilities in the
  appropriate directions. Examples of these are
  models of cellular metabolism, motility, global
  transcription regulation and differentiation, and
  life-cycle development. Each of these models
  could play a role in advancing toward the
  overarching goal of a complete cell model that
  can be used to predict phenotypic traits or
  behaviors of a cell from genomic and other omic
  data sources.

8
Need for a follow-up Study

• Recommendation 2 implies the need for a follow-up
  joint study that brings together the two
  communities.
• Recommendation 2. DOE should develop an explicit
  research program aimed at achieving significant
  progress on the overarching goal of predictive
  modeling and simulation in DOE relevant
  biological systems. This program should be a
  joint effort between ASCR and BER and should
  include a diversity of modeling approaches.
• The program should leverage existing
  experimental activities as well as support the
  development of new experimental activities that
  are directly tied to the needs of developing
  predictive models. This new research program
  should be aimed at advancing the state of the art
  of cell modeling directly, should include equal
  participation from biologists and mathematicians,
  computer scientists, and engineers and should be
  indirectly coupled to the more applied goals of
  bioenergy, carbon cycle research, or
  bioremediation.
• This program will need to be supported at a
  large-enough scale that a multiple-target
  approach can be pursued that will enable progress
  on many intermediate goals simultaneously by
  different research groups.
• This needs to be community driven.