Prashanth Suravajhala Keynote address at #BCC2020

1. 1
prash@bioclues.org
@prashbio
Open Minds Bring Open
Collaborations

2. 2
Grateful to four
Gs Galaxy ( James Taylor)
 Gandhiji

Genomes
 Gurus

3. Birla Institute of Scientific Research
1
3

4. Dr. Purnendu Ghosh, Executive Director
Dr. Krishna Mohan, Head, R & D
14 scientists
7 PhD fellows
2 Postdocs
Birla Institute of Scientific Research
1
4

5. 5
Stories
How open are we? The making of three Cs
1
2 Systems Genomics meets Serendipity! Identifying lncRNAs
from exomes
3
SARS-CoV-2 hijacking of mitochondria and role of lncRNAs

6. 6

7. 7
PROBLEM
Increasing incidence rate of predatory
publishing!
8 in 10 student researchers do NOT know what
Committee On Publication Ethics (COPE) is1
2 Lack of STEM curriculum hinders students to take up Math
logic/bioinformatics
3 Women mentees needed the most attention

8. 8
We love to talk about publications,
seldom do we discuss failures
80% of the reasons are just because of
Confidential
Do we engage the
scientific
community? Capacity building
mentor-
mentee
relationships
Monitoring
No: 20% No: 10% No: 40% No: 10%
Source [4, 5, 6]
Publish or Perish
Perform AND Publish
-

9. WHAT WE
NEEDED...
Collaborations
Diversity Inclusivene
ss
Convergenc
e
How good
listeners are
we?
Control over
mind
9

10. Over 4000 active members
2000 of them virtually mentored
Several Bioclues interest groups (BIG)
Women in Biology(WiB) forum
Over 25 publications
Thriving ‘Bio’community!
BIOinformatics CLUb for Experimenting Scientists
(BIOCLUES)
Pritish
Board
President: Narahari G Sastry, Director, CSIR-
NEIST.
Secretary: Devendra Biswal, NEHU Shillong.
Joint Secretary: Sugunakar Vuree
Immediate past president: Jayaraman K Valadi
Finance chairs: Harpreet Singh and Manuj
Agarwal
Women in Biology chairs: Sakshi Singh and
Aparna Banerjee
Outreach chairs: Hirakjyoti Das and Sujata Dhar
10

11. 11
What we do?
Bridging mentor-mentee relationships
2. Connect a mentor and ideate a
project
Telephony Online
discussions/Ideati
on challenges
Discussing and
liaiosining with
industries
Milestone mapping!
Openness
1. Identify prospective mentee
Set the
timelines
Tasking!

12. 12

13. Hippocratic Oath for scientists
1. Advocate for science, not (y)ourself
2. Focus on the merit of other publications, not self-approbating
(y)our
publications
3. Be creative and define success by practising introspection
4. Reconsider review of (y)our research
5. Persistence is the key: Pass on the baton to the next
generation
Aiming to keep the research vitality in the best interests of
I
Swea
r
First Do No Harm For Science
Image courtesy of
Hippocrates: Wikimedia
13

14. The current challenges in
Publishing/Peer-review
What is NOW! What OUGHT to be
Farce/Facade Publishing! Open Acess/Preprints
Diminishing fair peer-review Open up the peer-review policies
Self-citations “Sci”tations matter!
Flabbergasting h-index? h-index + Collaborative index (c-index)
14

15. 1. James =115 co-authors
2. Ask how many of these
co-authors in turn has
co-authors including
James ( n!-1)
3. Sum the list
4. C-index ~= 87
Come C-index!
C=87
15

16. 16

17. Part 1:
Conclusions
Launched
October 2, 2005
Mentorin
g 2006
Fellowshi
ps 2008
Women in Biology
APBioNet/ISCB
2009
BIRD
Awards
2010
IJCB
Journal
2011
Cloud based
Servers
2012
2016
Student
chapters
Bioinformatics
for schools
COMPLETED ON SCHEDULE PROPOSED
Founded
2019-Till end
Galaxy-Bioclues
2030
Bioclues
Vision Group
(BioVig)
transformed
17

18. 18
Stories
How open are we? The making of three Cs
1
2 Systems Genomics meets Serendipity! Identifying LncRNAs
from Exomes
3
SARS-CoV-2 hijacking of mitochondria
and role of lncRNAs

19. - Screened and annotated HPs in human (7540). Now 1408..1012!
- Found one of the HPs similar to MLH1 [mismatch repair protein]
- Proposed 'hypothome' [collection of hypothetical interactions
of predicted proteins]
- Used whole genome to exome data
- Ain’t any ncRNAs?
Bioinformation 2007
BMC Bioinformatics 2009
Int J Bioinform Res Appl. 2014
Syst Synth Biol. 2014
Protein and Peptide Letters,
2018.
So far experiments
haven’t led to
confirmation
of computational
predictions
http://www.pdra.org/wp-content/uploads/2015/10/102815-Failure-21.jpg
Q: What is the function of hypothetical
proteins?
Known knowns Unknown
knowns
Knowns unknowns Unknown
unknowns
TP: FN
TN: FN
There are ….. in the genomes
as well!

20. key outcome : Hypo2 server
1015 manually
curated records
integrated search
tools BLAST and
Performance Vector
through Decision
Trees
selection of DB
[UniProt/
TrEMBL/Swiss-Prot]
Potential biomarkers
http://www.bioclues.org/hypo2/

21. The known unknowns could be “noncoding RNAs”
The ncRNAs could have coding potential
The lncRNAs have special place for regulation and non-conservation makes them to serve as
effective biomarkers
The coding potential of ncRNAs could play a role in interaction studies
Hypothetical proteins as predecessors of lncRNAs
The interaction studies pave way for understanding regulation
Why not ncRNA-DNA/gene interactions?
Quick summary

22. Our problem with a rare phenotype
Congenital pouch colon (CPC) is a rare anorectal malformation in which
the colon ends in a pouch-like dilatation, which communicates with the
genitourinary system through a large fistula.

23. Number of candidate variants in the form of (a) coding sequences and (b) “heterozygous” mutations filtered against variati
Mathur et al. 2018. Scientific Reports

25. gupta.sonal1990@gmail.com
Case B: lnc-EPB41-Protein Interactions in
Congenital Pouch Colon
PROTEIN NAME MOLECULAR
WEIGHT
ACCESSION ID
interleukin-33 isoform a precursor 33 KDa NP_001300973.1
zinc finger protein 346 isoform b 35 KDa NP_001295142.1
butyrophilin subfamily 1 member
A1 precursor
57 KDa NP_001723.2
kinesin-like protein KIF13A
isoform d
202.3 KDa NP_001099038.1
PAN2-PAN3 deadenylation complex
catalytic subunit PAN2 isoform 2
135 KDa25 NP_001159751.1
pikachurin isoform 2 85 KDa NP_877950.1
PROTEINS INTERACTING WITH lncRNA
25
Identifying mutations in silico
NGS DOWNSTREAM FILE (vcf)
lncRNA-protein Interactions using
RPI-Pred and lncPro
(Suresh et al. 2015; Lu et al., 2013)
Find lncRNA (lnc-EPB41-1)
Gupta S et al. Biomolecules 2018
Smith-waterman algorithm, BBH
KIF13A
lnc-EPB41

26. lnc-EPB41-PROTEIN (KIF13A) INFERRED IN AFFECTED TISSUE COMPARED TO WILD TYPE USING MICROSCALE THERMOPHORESIS!
Gupta S et al. (2018). Biomolecules.
(a) Affected lnc-EPB41-protein interaction showing Kd obtained as 30nM±11.6nM with S/N ratio:10
(b) Wild type lnc-EPB41-protein interaction showing weak/no interaction

28. LncRNAs from exomes are a reality ( Myth busted! )
Due to the interactions in affected samples, there is a possibility that the pathways could be
altered in CPC.
lnc-EPB41-1-1 are known to be largely expressed in prostate and non-functional pituitary
adenomas (NFPA) supporting its regulatory role in urological/colonic tissues.
The lnc-EPB41-1-1 harbors two potential open chromatin elements OCE, viz.
ENSR00000003936 and ENSR00000003937 (E74-like factor 1, Ets family members respectively)
linking it with a regulatory role.
Conclusions of Part 2: LncRNAs from Exomes

29. 5
Stories
How open are we? The making of three Cs
1
2 Systems Genomics meets Serendipity! Identifying LncRNAs from
Exomes
3
SARS-CoV-2 hijacking of mitochondria and role of
lncRNAs

31. Target the non-structural proteins,
not just
Structural!
(M-E-N-S)
Epitopes
Ag determining sites
Targeting Abs/Aptamers

32. Overview of genes present in CoV-1 and Cov-2. Orf3b is one such gene
absent in Cov-2
Orf1ab
SARS-Cov-1
SARS-Cov-2
S 3a
3
b E 6
8
a NM
7
a
7
b
8
b
9b
Orf1ab S 3a E 6
8
a NM
7
a
7
b
8
b
9b
Mt image courtesy: https://www.pinterest.com/pin/342132902
916380956/

33. (a): Characteristic LXXC motif seen in Orf3a from multiple sequence alignment of various strains. The LWLC is known to be associated
with viral expression while CWLC is the motif seen in CoV-1. (b). Conserved CoV-1 sequences of Orf3b. The header of alignment shows
the amino acid positions highlighting non-consensus sequences.
(b). Orf3b
(a). Orf3a
240

34. : Characteristic ADNK motif exchange seen in Orf7a, highly conserved among COV-1 and CoV-2. (b) Orf7b with
characteristic LEXQDXX motif with good epitope sites. The header of alignment shows the amino acid positions highlighting
non-consensus sequences.
Orf7a
Orf7b

35. Figure 4 : Orf8 with characteristic CXXE motif for good epitope sites. The header of alignment shows
the amino acid positions highlighting non-consensus sequences.
Orf8

36. : Orf9b with characteristic DAXX motif for good epitope sites. The header of alignment shows the
amino acid positions highlighting non-consensus sequences.
Orf9b

37. NONHSAT239888. Highly expressed in Prostate
NONHSAT257828, NONHSAT257829, and NONHSAT257830.

38. 5
The diagnosis could be as simple as a
Pregnancy Test
Non-invasive test
Visual result within minutes
Simple and easy to perform
Prostate Cancer
detection

39. Conclusions for Part 3
Sequence variability could be questioned as many sequences keep arising i
Need for bringing the challenge of understanding epitopes and antigenic de
 Annotation and Curation for better Antibody/Aptamers (nsp10)
 LncRNAs as keyplayers showing association with Mitochondrial hijack of Co
We need raw sequences/meta data from the genomes and there aren’t man
IL-17a in addition to ACE-2 could be a master receptor. It’s association with

40. Overall
conclusions

41. Manuel et al. 2020
https://www.sciencedirect.c
om/science/article/pii/S004
8969720323305
Let's strive for cleaner environment, from #home to #office.
#NoToPlastic #SaveEnergy #SwitchoffTheVehicle at the red light
#traffic zone etc. Let's keep our #Lab and #WorkingSpace clean.
Small things would make immense difference! Most importantly,
let's clean our phone and computer by removing unused apps
and files. #BigDataChallenge
Where is COVID19 taking us as researchers?
What advice would you give as a researcher for someone treated/affected "with
virus" and "from virus“ Let’s make a good habit to live with it

42. Galaxy, BoF India
BoF India talk by Anshu and
Harpreet in
ca. 10 hrs from now ( 1830 hrs IST)
Kiran-Pratik-Sonika as our international
advisors
Anshu Bharadwaj,
IMTECH
BoF India leader
GN Sastry, Director, NEIST and President,
Bioclues
Harpreet Singh, HMV,
Jalandhar
Coordinator, Galaxy India
and Finance Secretary,
Bioclues
Devendra K Biswal,
NEHU, Shillong and
Secretary, Bioclues
Rep, NE India
Sangram Sahu
Rep, South India

43. Thank you Asif , Dave, Gareth, and Team
BCC/Galaxy
Looking forward to Converge
Group page: http://www.bioinformatics.org/wiki/Prash
prash@bisr.res.in or prash@bioclues.org
Functional/Structural Biology
•PB Kavi Kishor, Vignan, Guntur
•Ratnagiri Polavarapu, Genomix CARL
•G Padmanabhan, IISc, Bengaluru
•VA Nagaraj, ILS, Bhubaneshwar
•Abhinav Parashar, Vignan, Guntur
•Renuka Suravajhala, MUJ, Jaipur
Medical Genomics
•Keshav K Singh, UAB, USA
•Gyaneshwar Chaubey, BHU, Varanasi
•Uma Kanga, AIIMS, Delhi
•Praveen Mathur, SMSMC, Jaipur
•Krishna Mohan Medicherla, BISR,
Jaipur
PhD fellows and Postdoc
Sonal Gupta ( PhD), Postdoc
Ayam Gupta, PhD fellow
Nidhi Shukla, PhD fellow
Anchita Prasad, Phd fellow
Harshita Bhargava, PhD fellow
Purva Bhalothia, PhD. Postdoc
Machine Learning Heuristics
PritishVaradwaj, PhD,IIIT Allahabad
Jayaraman K Valadi, PhD, FLAME
University
Jeff W Bizzar, Bioinformatics.org
Open Source community
Brainpain.co ( Saurabh and Amrit)
Family
Near and dear