in reply to problems with backreference
\1 is a regular expression pattern that matches what the first capture captured. It makes no sense to use it outside of regular expressions as you did.
Perl script:
s/^(ISA\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~)(..........)(....).(\~.*) +$/$1${2}0$3$4/
Perl command:
perl -i -pe's/^(ISA\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~)(..........)( +....).(\~.*)$/$1${2}0$3$4/' PB385930.P0
ssh command:
ssh ... 'perl -i -pe'\''s/^(ISA\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~.*?\~)( +..........)(....).(\~.*)$/$1${2}0$3$4/'\'' PB385930.P0'
Note the ' needed to be escaped when placed inside another ' literal.
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Seekers of Perl Wisdom